Human DNA ligases I and IIIα as determinants of accuracy and efficiency of base excision DNA repair .
Academic Journal
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Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 1264604 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1638-6183 (Electronic) Linking ISSN: 03009084 NLM ISO Abbreviation: Biochimie Subsets: MEDLINE
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Moor NA;Vasil'eva IA;Lavrik OI
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Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 1264604 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1638-6183 (Electronic) Linking ISSN: 03009084 NLM ISO Abbreviation: Biochimie Subsets: MEDLINE
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Mammalian Base Excision Repair (BER) DNA ligases I and IIIα (LigI, LigIIIα) are major ...
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Human DNA ligases I and IIIα as determinants of accuracy and efficiency of base excision DNA repair .
Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 1264604 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1638-6183 (Electronic) Linking ISSN: 03009084 NLM ISO Abbreviation: Biochimie Subsets: MEDLINE
Mammalian Base Excision Repair (BER) DNA ligases I and IIIα (LigI, LigIIIα) are major determinants of DNA repair fidelity, alongside with DNA polymerases. Here we compared activities of human LigI and LigIIIα on specific and nonspecific substrates representing intermediates of distinct BER sub-pathways. The enzymes differently discriminate mismatches in the nicked DNA , depending on their identity and position, but are both more selective against the 3'-end non-complementarity. LigIIIα is less active than LigI in premature ligation of one-nucleotide gapped DNA and more efficiently discriminates misinsertion products of DNA polymerase β-catalyzed gap filling, that reinforces a leading role of LigIIIα in the accuracy of short-patch BER. LigI and LigIIIα reseal the intermediate of long-patch BER containing an incised synthetic AP site (F) with different efficiencies, depending on the DNA sequence context, 3'-end mismatch presence and coupling of the ligation reaction with DNA repair synthesis. Processing of this intermediate in the absence of flap endonuclease 1 generates non-canonical DNAs with bulged F site, which are very inefficiently repaired by AP endonuclease 1 and represent potential mutagenic repair products. The extent of conversion of the 5'-adenylated intermediates of specific and nonspecific substrates is revealed to depend on the DNA sequence context; a higher sensitivity of LigI to the sequence is in line with the enzyme structural feature of DNA binding. LigIIIα exceeds LigI in generation of potential abortive ligation products, justifying importance of XRCC1-mediated coordination of LigIIIα and aprataxin activities for the efficient DNA repair .
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)
Subject terms:
Animals - Humans - DNA genetics - DNA metabolism - DNA-Directed DNA Polymerase metabolism - DNA Ligases genetics - DNA Ligases metabolism - Excision Repair - Mammals metabolism - X-ray Repair Cross Complementing Protein 1 genetics - X-ray Repair Cross Complementing Protein 1 metabolism - DNA Repair - DNA Polymerase beta genetics - DNA Polymerase beta metabolismContent provider:
MEDLINE
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Exploring DNA repair deficient CHO cell response to low dose rate radiation.
Academic Journal
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Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
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Buglewicz DJ;Haskins JS;Haskins AH;Su C;Gius JP;Kato TA
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Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
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Introduction: DNA double-strand breaks (DSBs) induced by ionizing radiation pose a sig...
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Exploring DNA repair deficient CHO cell response to low dose rate radiation.
Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
Introduction: DNA double-strand breaks (DSBs) induced by ionizing radiation pose a significant threat to genome integrity, necessitating robust repair mechanisms. This study explores the responses of repair -deficient cells to low dose rate (LDR) radiation. Non-homologous end joining (NHEJ) and homologous recombination (HR) repair pathways play pivotal roles in maintaining genomic stability. The hypothesis posits distinct cellular outcomes under LDR exposure compared to acute radiation, impacting DNA repair mechanisms and cell survival.
Materials and Methods: Chinese hamster ovary (CHO) cells, featuring deficiencies in NHEJ, HR, Fanconi Anemia, and PARP pathways, were systematically studied. Clonogenic assays for acute and LDR gamma-ray exposures, cell growth inhibition analyses, and γ-H2AX foci assays were conducted, encompassing varied dose rates to comprehensively assess cellular responses.
Results: NHEJ mutants exhibited an unexpected inverse dose rate effect, challenging conventional expectations. HR mutants displayed unique radiosensitivity patterns, aligning with responses to majorDNA -damaging agents. LDR exposure induced cell cycle alterations, growth delays, and giant cell formation, revealing context-dependent sensitivities. γ-H2AX foci assays indicated DSB accumulation during LDR exposure.
Discussion: These findings challenge established paradigms, emphasizing the intricate interplay betweenrepair pathways and dose rates. The study offers comprehensive insights into repair -deficient cell responses, urging a reevaluation of conventional dose-response models and providing potential avenues for targeted therapeutic strategies in diverse radiation scenarios.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Takamitsu Kato reports financial support was provided by Dr Akiko Ueno Radiobiology Research Fund. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Materials and Methods: Chinese hamster ovary (CHO) cells, featuring deficiencies in NHEJ, HR, Fanconi Anemia, and PARP pathways, were systematically studied. Clonogenic assays for acute and LDR gamma-ray exposures, cell growth inhibition analyses, and γ-H2AX foci assays were conducted, encompassing varied dose rates to comprehensively assess cellular responses.
Results: NHEJ mutants exhibited an unexpected inverse dose rate effect, challenging conventional expectations. HR mutants displayed unique radiosensitivity patterns, aligning with responses to major
Discussion: These findings challenge established paradigms, emphasizing the intricate interplay between
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Takamitsu Kato reports financial support was provided by Dr Akiko Ueno Radiobiology Research Fund. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Subject terms:
Cricetinae - Animals - CHO Cells - Cricetulus - Recombinational DNA Repair - DNA - DNA Repair genetics - DNA End-Joining Repair geneticsContent provider:
MEDLINE
Developmental progression of DNA double-strand break repair deciphered by a single-allele resolution mutation classifier.
Academic Journal
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Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
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Li Z;You L;Hermann A;Bier E
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Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
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DNA double-strand breaks (DSBs) are repaired by a hierarchically regulated network of ...
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Developmental progression of DNA double-strand break repair deciphered by a single-allele resolution mutation classifier.
DNA double-strand breaks (DSBs) are repaired by a hierarchically regulated network of pathways. Factors influencing the choice of particular repair pathways, however remain poorly characterized. Here we develop an Integrated Classification Pipeline (ICP) to decompose and categorize CRISPR/Cas9 generated mutations on genomic target sites in complex multicellular insects. The ICP outputs graphic rank ordered classifications of mutant alleles to visualize discriminating DSB repair fingerprints generated from different target sites and alternative inheritance patterns of CRISPR components. We uncover highly reproducible lineage-specific mutation fingerprints in individual organisms and a developmental progression wherein Microhomology-Mediated End-Joining (MMEJ) or Insertion events predominate during early rapid mitotic cell cycles, switching to distinct subsets of Non-Homologous End-Joining (NHEJ) alleles, and then to Homology-Directed Repair (HDR)-based gene conversion. These repair signatures enable marker-free tracking of specific mutations in dynamic populations, including NHEJ and HDR events within the same samples, for in-depth analysis of diverse gene editing events.
(© 2024. The Author(s).)
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
(© 2024. The Author(s).)
Subject terms:
Alleles - DNA metabolism - DNA End-Joining Repair - Mutation - Recombinational DNA Repair - CRISPR-Cas Systems genetics - DNA Breaks, Double-Stranded - DNA Repair geneticsContent provider:
MEDLINE
Functional screening in human HSPCs identifies optimized protein-based enhancers of Homology Directed Repair .
Academic Journal
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Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
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Perez-Bermejo JA;Efagene O;Matern WM;Holden JK;Kabir S;Chew GM;Andreoletti ...
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Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
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Homology Directed Repair (HDR) enables precise genome editing, but the implementation ...
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Functional screening in human HSPCs identifies optimized protein-based enhancers of Homology Directed Repair .
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Homology Directed Repair (HDR) enables precise genome editing, but the implementation of HDR-based therapies is hindered by limited efficiency in comparison to methods that exploit alternative DNA repair routes, such as Non-Homologous End Joining (NHEJ). In this study, we develop a functional, pooled screening platform to identify protein-based reagents that improve HDR in human hematopoietic stem and progenitor cells (HSPCs). We leverage this screening platform to explore sequence diversity at the binding interface of the NHEJ inhibitor i53 and its target, 53BP1, identifying optimized variants that enable new intermolecular bonds and robustly increase HDR. We show that these variants specifically reduce insertion-deletion outcomes without increasing off-target editing, synergize with a DNAPK inhibitor molecule, and can be applied at manufacturing scale to increase the fraction of cells bearing repaired alleles. This screening platform can enable the discovery of future gene editing reagents that improve HDR outcomes.
(© 2024. The Author(s).)
(© 2024. The Author(s).)
Subject terms:
Humans - Gene Editing methods - DNA Repair - DNA End-Joining Repair - CRISPR-Cas Systems - Recombinational DNA RepairContent provider:
MEDLINE
Quantitative, titratable and high-throughput reporter assays to measure DNA double strand break repair activity in cells.
Academic Journal
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Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
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Rajendra E;Grande D;Mason B;Di Marcantonio D;Armstrong L;Hewitt G;Elinati E...
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Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
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Repair of DNA damage is essential for the maintenance of genome stability and cell via...
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Quantitative, titratable and high-throughput reporter assays to measure DNA double strand break repair activity in cells.
Repair of DNA damage is essential for the maintenance of genome stability and cell viability. DNA double strand breaks (DSBs) constitute a toxic class of DNA lesion and multiple cellular pathways exist to mediate their repair . Robust and titratable assays of cellular DSB repair (DSBR) are important to functionally interrogate the integrity and efficiency of these mechanisms in disease models as well as in response to genetic or pharmacological perturbations. Several variants of DSBR reporters are available, however these are often limited by throughput or restricted to specific cellular models. Here, we describe the generation and validation of a suite of extrachromosomal reporter assays that can efficiently measure the major DSBR pathways of homologous recombination (HR), classical nonhomologous end joining (cNHEJ), microhomology-mediated end joining (MMEJ) and single strand annealing (SSA). We demonstrate that these assays can be adapted to a high-throughput screening format and that they are sensitive to pharmacological modulation, thus providing mechanistic and quantitative insights into compound potency, selectivity, and on-target specificity. We propose that these reporter assays can serve as tools to dissect the interplay of DSBR pathway networks in cells and will have broad implications for studies of DSBR mechanisms in basic research and drug discovery.
(© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
(© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Subject terms:
DNA metabolism - DNA Breaks, Double-Stranded - DNA End-Joining Repair - Homologous Recombination - Recombinational DNA Repair - Humans - Cell Line - DNA Repair genetics - High-Throughput Screening AssaysContent provider:
MEDLINE
Generation of site-specifically labelled fluorescent human XPA to investigate DNA binding dynamics during nucleotide excision repair .
Academic Journal
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Publisher: Academic Press Country of Publication: United States NLM ID: 9426302 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9130 (Electronic) Linking ISSN: 10462023 NLM ISO Abbreviation: Methods Subsets: MEDLINE
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Kuppa S;Corless E;Caldwell CC;Spies M;Antony E
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Publisher: Academic Press Country of Publication: United States NLM ID: 9426302 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9130 (Electronic) Linking ISSN: 10462023 NLM ISO Abbreviation: Methods Subsets: MEDLINE
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Nucleotide excision repair (NER) promotes genomic integrity by removing bulky DNA addu...
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Generation of site-specifically labelled fluorescent human XPA to investigate DNA binding dynamics during nucleotide excision repair .
Publisher: Academic Press Country of Publication: United States NLM ID: 9426302 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-9130 (Electronic) Linking ISSN: 10462023 NLM ISO Abbreviation: Methods Subsets: MEDLINE
Nucleotide excision repair (NER) promotes genomic integrity by removing bulky DNA adducts introduced by external factors such as ultraviolet light. Defects in NER enzymes are associated with pathological conditions such as Xeroderma Pigmentosum, trichothiodystrophy, and Cockayne syndrome. A critical step in NER is the binding of the Xeroderma Pigmentosum group A protein (XPA) to the ss/ds DNA junction. To better capture the dynamics of XPA interactions with DNA during NER we have utilized the fluorescence enhancement through non-canonical amino acids (FEncAA) approach. 4-azido-L-phenylalanine (4AZP or pAzF) was incorporated at Arg-158 in human XPA and conjugated to Cy3 using strain-promoted azide-alkyne cycloaddition. The resulting fluorescent XPA protein (XPA Cy3 ) shows no loss in DNA binding activity and generates a robust change in fluorescence upon binding to DNA . Here we describe methods to generate XPA Cy3 and detail in vitro experimental conditions required to stably maintain the protein during biochemical and biophysical studies.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Inc.)
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Inc.)
Subject terms:
Humans - Excision Repair - Xeroderma Pigmentosum Group A Protein genetics - Xeroderma Pigmentosum Group A Protein chemistry - Xeroderma Pigmentosum Group A Protein metabolism - DNA chemistry - Ultraviolet Rays - Nucleotides - Protein Binding - DNA Repair genetics - DNA Damage geneticsContent provider:
MEDLINE
DNA repair, genetic instability, and cancer / editors, Qingyi Wei, Lei Li, David J. Chen.
Book
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2007
Available at Available Merrill-Cazier Books (3rd Floor North) (Call number: QH 467 .D164 2007)
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| Location | Call No. | Status |
|---|---|---|
| Merrill-Cazier Books (3rd Floor North) | QH 467 .D164 2007 | Available |
Structural role for DNA Ligase IV in promoting the fidelity of non-homologous end joining.
Academic Journal
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Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
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Stinson BM;Carney SM;Walter JC;Loparo JJ
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Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
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Nonhomologous end joining (NHEJ), the primary pathway of vertebrate DNA double-strand-...
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Structural role for DNA Ligase IV in promoting the fidelity of non-homologous end joining.
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Nonhomologous end joining (NHEJ), the primary pathway of vertebrate DNA double-strand-break (DSB) repair , directly re-ligates broken DNA ends. Damaged DSB ends that cannot be immediately re-ligated are modified by NHEJ processing enzymes, including error-prone polymerases and nucleases, to enable ligation. However, DSB ends that are initially compatible for re-ligation are typically joined without end processing. As both ligation and end processing occur in the short-range (SR) synaptic complex that closely aligns DNA ends, it remains unclear how ligation of compatible ends is prioritized over end processing. In this study, we identify structural interactions of the NHEJ-specific DNA Ligase IV (Lig4) within the SR complex that prioritize ligation and promote NHEJ fidelity. Mutational analysis demonstrates that Lig4 must bind DNA ends to form the SR complex. Furthermore, single-molecule experiments show that a single Lig4 binds both DNA ends at the instant of SR synapsis. Thus, Lig4 is poised to ligate compatible ends upon initial formation of the SR complex before error-prone processing. Our results provide a molecular basis for the fidelity of NHEJ.
(© 2024. The Author(s).)
(© 2024. The Author(s).)
Subject terms:
DNA Ligase ATP metabolism - DNA Repair - DNA Ligases metabolism - DNA genetics - DNA metabolism - DNA Breaks, Double-Stranded - DNA End-Joining RepairContent provider:
MEDLINE
MutSβ protects common fragile sites by facilitating homology-directed repair at DNA double-strand breaks with secondary structures.
Academic Journal
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Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
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Li Y;Zhang Y;Shah SB;Chang CY;Wang H;Wu X
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Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
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Common fragile sites (CFSs) are regions prone to chromosomal rearrangements, thereby c...
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MutSβ protects common fragile sites by facilitating homology-directed repair at DNA double-strand breaks with secondary structures.
Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
Common fragile sites (CFSs) are regions prone to chromosomal rearrangements, thereby contributing to tumorigenesis. Under replication stress (RS), CFSs often harbor under-replicated DNA regions at the onset of mitosis, triggering homology-directed repair known as mitotic DNA synthesis (MiDAS) to complete DNA replication. In this study, we identified an important role of DNA mismatch repair protein MutSβ (MSH2/MSH3) in facilitating MiDAS and maintaining CFS stability. Specifically, we demonstrated that MutSβ is required for the increased mitotic recombination induced by RS or FANCM loss at CFS-derived AT-rich and structure-prone sequences (CFS-ATs). We also found that MSH3 exhibits synthetic lethality with FANCM. Mechanistically, MutSβ is required for homologous recombination (HR) especially when DNA double-strand break (DSB) ends contain secondary structures. We also showed that upon RS, MutSβ is recruited to Flex1, a specific CFS-AT, in a PCNA-dependent but MUS81-independent manner. Furthermore, MutSβ interacts with RAD52 and promotes RAD52 recruitment to Flex1 following MUS81-dependent fork cleavage. RAD52, in turn, recruits XPF/ERCC1 to remove DNA secondary structures at DSB ends, enabling HR/break-induced replication (BIR) at CFS-ATs. We propose that the specific requirement of MutSβ in processing DNA secondary structures at CFS-ATs underlies its crucial role in promoting MiDAS and maintaining CFS integrity.
(© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
(© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Subject terms:
DNA Replication genetics - Recombinational DNA Repair - DNA genetics - DNA metabolism - Proteins genetics - DNA Breaks, Double-Stranded - DNA Repair geneticsContent provider:
MEDLINE
AND Logic Gate-Regulated DNAzyme Nanoflower for Monitoring the Activity of Multiple DNA Repair Enzymes.
Academic Journal
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Publisher: American Chemical Society Country of Publication: United States NLM ID: 0370536 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-6882 (Electronic) Linking ISSN: 00032700 NLM ISO Abbreviation: Anal Chem Subsets: MEDLINE
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Zeng WJ;Li XR;Liu W;Yuan R;Liang WB;Zhuo Y
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Publisher: American Chemical Society Country of Publication: United States NLM ID: 0370536 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-6882 (Electronic) Linking ISSN: 00032700 NLM ISO Abbreviation: Anal Chem Subsets: MEDLINE
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Despite the progress that has been made in diverse DNA-based nanodevices to in situ mo...
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AND Logic Gate-Regulated DNAzyme Nanoflower for Monitoring the Activity of Multiple DNA Repair Enzymes.
Publisher: American Chemical Society Country of Publication: United States NLM ID: 0370536 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-6882 (Electronic) Linking ISSN: 00032700 NLM ISO Abbreviation: Anal Chem Subsets: MEDLINE
Despite the progress that has been made in diverse DNA -based nanodevices to in situ monitor the activity of the DNA repair enzymes in living cells, the significance of improving both the sensitivity and specificity has remained largely neglected and understudied. Herein, we propose a regulatable DNA nanodevice to specifically monitor the activity of DNA repair enzymes for early evaluation of cancer mediated by genomic instability. Concretely, an AND logic gate-regulated DNAzyme nanoflower was rationally designed by the self-assembly of the DNA duplex modified with both apurinic/apyrimidinic (AP) site and methyl lesion site. The DNAzyme nanoflower could be reconfigured under the repair of AP sites and O 6 -methylguanine sites by apurinic/apyrimidinic endonuclease 1 (APE1) and O 6 -methylguanine methyltransferase (MGMT) to produce a fluorescent signal, realizing the sensitive monitoring of the activity of APE1 and MGMT. Compared to the free DNAzyme duplex, the fluorescent response of the DNAzyme nanoflower increased by 60%, due to the effective enrichment of the DNA probes by the nanoflower structure. More importantly, we have demonstrated that the dual-enzyme activated strategy allows imaging of specific cancer cells in the AND logic gate manner using MCF-7 as a cancer cell model, improving the specificity of cancer cell imaging. This AND logic gate-regulated multifunctional DNAzyme nanoflower provides a simple tool for simultaneously visualizing multiple DNA repair enzymes, holding great potential in early clinical diagnosis and drug discovery.
Subject terms:
DNA Damage - DNA Repair Enzymes genetics - DNA-(Apurinic or Apyrimidinic Site) Lyase metabolism - DNA chemistry - DNA Repair - DNA, CatalyticContent provider:
MEDLINE
Eukaryotic DNA damage surveillance and repair / Keith W. Caldecott.
Book
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2004
Available at Available Merrill-Cazier Books (3rd Floor North) (Call number: QH 465 .A1 C34 2004)
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| Location | Call No. | Status |
|---|---|---|
| Merrill-Cazier Books (3rd Floor North) | QH 465 .A1 C34 2004 | Available |
Ku80 is indispensable for repairing DNA double-strand breaks at highly methylated sites in human HCT116 cells.
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Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101139138 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1568-7856 (Electronic) Linking ISSN: 15687856 NLM ISO Abbreviation: DNA Repair (Amst) Subsets: MEDLINE
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Xing M;Xiong Y;Zhang Y
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Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101139138 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1568-7856 (Electronic) Linking ISSN: 15687856 NLM ISO Abbreviation: DNA Repair (Amst) Subsets: MEDLINE
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DNA double-strand breaks (DSBs) are harmful to mammalian cells and a few of them can c...
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Ku80 is indispensable for repairing DNA double-strand breaks at highly methylated sites in human HCT116 cells.
DNA double-strand breaks (DSBs) are harmful to mammalian cells and a few of them can cause cell death. Accumulating DSBs in these cells to analyze their genomic distribution and their potential impact on chromatin structure is difficult. In this study, we used CRISPR to generate Ku80 -/- human cells and arrested the cells in G1 phase to accumulate DSBs before conducting END-seq and Nanopore analysis. Our analysis revealed that DNA with high methylation level accumulates DSB hotspots in Ku80 -/- human cells. Furthermore, we identified chromosome structural variants (SVs) using Nanopore sequencing and observed a higher number of SVs in Ku80 -/- human cells. Based on our findings, we suggest that the high efficiency of Ku80 knockout in human HCT116 cells makes it a promising model for characterizing SVs in the context of 3D chromatin structure and studying the alternative-end joining (Alt-EJ) DSB repair pathway.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101139138 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1568-7856 (Electronic) Linking ISSN: 15687856 NLM ISO Abbreviation: DNA Repair (Amst) Subsets: MEDLINE
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Subject terms:
Animals - Humans - Chromatin - DNA - DNA End-Joining Repair - HCT116 Cells - Mammals metabolism - DNA Breaks, Double-Stranded - DNA Repair genetics - Ku Autoantigen genetics - Ku Autoantigen metabolismContent provider:
MEDLINE
DNA repair.
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| Holdings | v.1 (2002) - v.6 (2007) |
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PRMT5-mediated homologous recombination repair is essential to maintain genomic integrity of neural progenitor cells.
Academic Journal
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Publisher: Springer Country of Publication: Switzerland NLM ID: 9705402 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-9071 (Electronic) Linking ISSN: 1420682X NLM ISO Abbreviation: Cell Mol Life Sci Subsets: MEDLINE
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Wang YJ;Cao JB;Yang J;Liu T;Yu HL;He ZX;Bao SL;He XX;Zhu XJ
Academic Journal
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Publisher: Springer Country of Publication: Switzerland NLM ID: 9705402 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-9071 (Electronic) Linking ISSN: 1420682X NLM ISO Abbreviation: Cell Mol Life Sci Subsets: MEDLINE
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Maintaining genomic stability is a prerequisite for proliferating NPCs to ensure genet...
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PRMT5-mediated homologous recombination repair is essential to maintain genomic integrity of neural progenitor cells.
Publisher: Springer Country of Publication: Switzerland NLM ID: 9705402 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-9071 (Electronic) Linking ISSN: 1420682X NLM ISO Abbreviation: Cell Mol Life Sci Subsets: MEDLINE
Maintaining genomic stability is a prerequisite for proliferating NPCs to ensure genetic fidelity. Though histone arginine methylation has been shown to play important roles in safeguarding genomic stability, the underlying mechanism during brain development is not fully understood. Protein arginine N-methyltransferase 5 (PRMT5) is a type II protein arginine methyltransferase that plays a role in transcriptional regulation. Here, we identify PRMT5 as a key regulator of DNA repair in response to double-strand breaks (DSBs) during NPC proliferation. Prmt5 F/F ; Emx1-Cre (cKO-Emx1) mice show a distinctive microcephaly phenotype, with partial loss of the dorsal medial cerebral cortex and complete loss of the corpus callosum and hippocampus. This phenotype is resulted from DSBs accumulation in the medial dorsal cortex followed by cell apoptosis. Both RNA sequencing and in vitro DNA repair analyses reveal that PRMT5 is required for DNA homologous recombination (HR) repair . PRMT5 specifically catalyzes H3R2me2s in proliferating NPCs in the developing mouse brain to enhance HR-related gene expression during DNA repair . Finally, overexpression of BRCA1 significantly rescues DSBs accumulation and cell apoptosis in PRMT5-deficient NSCs. Taken together, our results show that PRMT5 maintains genomic stability by regulating histone arginine methylation in proliferating NPCs.
(© 2024. The Author(s).)
(© 2024. The Author(s).)
Subject terms:
Animals - Mice - Arginine metabolism - DNA Repair - Genomic Instability - Genomics - Histones genetics - Histones metabolism - Protein-Arginine N-Methyltransferases genetics - Protein-Arginine N-Methyltransferases metabolism - Neural Stem Cells metabolism - Recombinational DNA RepairContent provider:
MEDLINE
Advances in DNA damage and repair : oxygen radical effects, cellular protection, and biological consequences / edited by Miral Dizdaroglu and Ali Esat Karakaya.
Book
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1999
Available at Available Merrill-Cazier Books (3rd Floor North) (Call number: QH 465 .A1 A36 1999)
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| Location | Call No. | Status |
|---|---|---|
| Merrill-Cazier Books (3rd Floor North) | QH 465 .A1 A36 1999 | Available |
Site-specific acetylation of polynucleotide kinase 3'-phosphatase regulates its distinct role in DNA repair pathways.
Academic Journal
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Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
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Islam A;Chakraborty A;Sarker AH;Aryal UK;Pan L;Sharma G;Boldogh I;Hazra T
Academic Journal
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Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
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Mammalian polynucleotide kinase 3'-phosphatase (PNKP), a DNA end-processing enzyme wit...
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Site-specific acetylation of polynucleotide kinase 3'-phosphatase regulates its distinct role in DNA repair pathways.
Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
Mammalian polynucleotide kinase 3'-phosphatase (PNKP), a DNA end-processing enzyme with 3'-phosphatase and 5'-kinase activities, is involved in multiple DNA repair pathways, including base excision (BER), single-strand break (SSBR), and double-strand break repair (DSBR). However, little is known as to how PNKP functions in such diverse repair processes. Here we report that PNKP is acetylated at K142 (AcK142) by p300 constitutively but at K226 (AcK226) by CBP, only after DSB induction. Co-immunoprecipitation analysis using AcK142 or AcK226 PNKP-specific antibodies showed that AcK142-PNKP associates only with BER/SSBR, and AcK226 PNKP with DSBR proteins. Despite the modest effect of acetylation on PNKP's enzymatic activity in vitro, cells expressing non-acetylable PNKP (K142R or K226R) accumulated DNA damage in transcribed genes. Intriguingly, in striatal neuronal cells of a Huntington's Disease (HD)-based mouse model, K142, but not K226, was acetylated. This is consistent with the reported degradation of CBP, but not p300, in HD cells. Moreover, transcribed genomes of HD cells progressively accumulated DSBs. Chromatin-immunoprecipitation analysis demonstrated the association of Ac-PNKP with the transcribed genes, consistent with PNKP's role in transcription-coupled repair . Thus, our findings demonstrate that acetylation at two lysine residues, located in different domains of PNKP, regulates its distinct role in BER/SSBR versus DSBR.
(© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
(© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
