Regulation of DNA double-strand break repair pathway choice View Full Text


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Article Info

DATE

2007-12-24

AUTHORS

Meena Shrivastav, Leyma P De Haro, Jac A Nickoloff

ABSTRACT

DNA double-strand breaks (DSBs) are critical lesions that can result in cell death or a wide variety of genetic alterations including large- or small-scale deletions, loss of heterozygosity, translocations, and chromosome loss. DSBs are repaired by non-homologous end-joining (NHEJ) and homologous recombination (HR), and defects in these pathways cause genome instability and promote tumorigenesis. DSBs arise from endogenous sources including reactive oxygen species generated during cellular metabolism, collapsed replication forks, and nucleases, and from exogenous sources including ionizing radiation and chemicals that directly or indirectly damage DNA and are commonly used in cancer therapy. The DSB repair pathways appear to compete for DSBs, but the balance between them differs widely among species, between different cell types of a single species, and during different cell cycle phases of a single cell type. Here we review the regulatory factors that regulate DSB repair by NHEJ and HR in yeast and higher eukaryotes. These factors include regulated expression and phosphorylation of repair proteins, chromatin modulation of repair factor accessibility, and the availability of homologous repair templates. While most DSB repair proteins appear to function exclusively in NHEJ or HR, a number of proteins influence both pathways, including the MRE11/RAD50/NBS1(XRS2) complex, BRCA1, histone H2AX, PARP-1, RAD18, DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and ATM. DNA-PKcs plays a role in mammalian NHEJ, but it also influences HR through a complex regulatory network that may involve crosstalk with ATM, and the regulation of at least 12 proteins involved in HR that are phosphorylated by DNA-PKcs and/or ATM. More... »

PAGES

134-147

References to SciGraph publications

  • 1999-01. Yeast cell-type regulation of DNA repair in NATURE
  • 2004-01-22. Caffeine inhibits homology-directed repair of I-SceI-induced DNA double-strand breaks in ONCOGENE
  • 2000-02-03. Dissociation of p53-mediated suppression of homologous recombination from G1/S cell cycle checkpoint control in ONCOGENE
  • 2001-12. NEJ1 controls non-homologous end joining in Saccharomyces cerevisiae in NATURE
  • 2004-10. DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1 in NATURE
  • 2004-12-13. The life and death of DNA-PK in ONCOGENE
  • 2006-09-25. The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability in ONCOGENE
  • 2000-12. A role for Saccharomyces cerevisiae histone H2A in DNA repair in NATURE
  • 2006-06-14. ATM stabilizes DNA double-strand-break complexes during V(D)J recombination in NATURE
  • 2006-05. Regulation of DNA repair by ubiquitylation in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2007-11-18. A YY1–INO80 complex regulates genomic stability through homologous recombination–based repair in NATURE STRUCTURAL & MOLECULAR BIOLOGY
  • 2005-03. CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair in NATURE
  • 2007-03-26. Homologous recombination repair is regulated by domains at the N- and C-terminus of NBS1 and is dissociated with ATM functions in ONCOGENE
  • 2007-05-21. Stabilization of RAD51 nucleoprotein filaments by the C-terminal region of BRCA2 in NATURE STRUCTURAL & MOLECULAR BIOLOGY
  • 2004-10-18. The interaction of p53 with replication protein A mediates suppression of homologous recombination in ONCOGENE
  • 1997-04-17. Inactivation of p53 results in high rates of homologous recombination in ONCOGENE
  • 2003-06. Molecular views of recombination proteins and their control in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2002-10. Playing for half the deck: the molecular biology of meiosis. in NATURE CELL BIOLOGY
  • 2006-03-17. p53 in recombination and repair in CELL DEATH & DIFFERENTIATION
  • 1998. Nature of Lesions Formed by Ionizing Radiation in DNA DAMAGE AND REPAIR
  • 2001-01. SGS1, the Saccharomyces cerevisiae homologue of BLM and WRN, suppresses genome instability and homeologous recombination in NATURE GENETICS
  • 2007-06-20. Chromatin dynamics and the preservation of genetic information in NATURE
  • Journal

    TITLE

    Cell Research

    ISSUE

    1

    VOLUME

    18

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/cr.2007.111

    DOI

    http://dx.doi.org/10.1038/cr.2007.111

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/18157161


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    49 schema:description DNA double-strand breaks (DSBs) are critical lesions that can result in cell death or a wide variety of genetic alterations including large- or small-scale deletions, loss of heterozygosity, translocations, and chromosome loss. DSBs are repaired by non-homologous end-joining (NHEJ) and homologous recombination (HR), and defects in these pathways cause genome instability and promote tumorigenesis. DSBs arise from endogenous sources including reactive oxygen species generated during cellular metabolism, collapsed replication forks, and nucleases, and from exogenous sources including ionizing radiation and chemicals that directly or indirectly damage DNA and are commonly used in cancer therapy. The DSB repair pathways appear to compete for DSBs, but the balance between them differs widely among species, between different cell types of a single species, and during different cell cycle phases of a single cell type. Here we review the regulatory factors that regulate DSB repair by NHEJ and HR in yeast and higher eukaryotes. These factors include regulated expression and phosphorylation of repair proteins, chromatin modulation of repair factor accessibility, and the availability of homologous repair templates. While most DSB repair proteins appear to function exclusively in NHEJ or HR, a number of proteins influence both pathways, including the MRE11/RAD50/NBS1(XRS2) complex, BRCA1, histone H2AX, PARP-1, RAD18, DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and ATM. DNA-PKcs plays a role in mammalian NHEJ, but it also influences HR through a complex regulatory network that may involve crosstalk with ATM, and the regulation of at least 12 proteins involved in HR that are phosphorylated by DNA-PKcs and/or ATM.
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    58 DNA double-strand breaks
    59 DNA-PKcs
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    74 cancer therapy
    75 catalytic subunit
    76 cell cycle phases
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    78 cell types
    79 cellular metabolism
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    81 choice
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    88 cycle phase
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    95 double-strand breaks
    96 endogenous sources
    97 eukaryotes
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    99 expression
    100 factor accessibility
    101 factors
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    104 genome instability
    105 heterozygosity
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    107 histone H2AX
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    114 mammalian NHEJ
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