Ku protein stimulates DNA end joining by mammalian DNA ligases: a direct role for Ku in repair of DNA double‐strand breaks

Ku protein binds to DNA ends and is a cofactor for the DNA‐dependent protein kinase. Both of these components are involved in DNA double‐strand break repair, but it has not been clear if they function indirectly, by sensing DNA damage and activating other factors, or if they are more directly involved in the processing and rejoining of DNA breaks. We demonstrate that intermolecular ligation of DNA fragments is highly dependent on Ku under conditions designed to mimic those existing in the cell. This effect of Ku is specific to eukaryotic DNA ligases. Ku protein, therefore, has an activity consistent with a direct role in rejoining DNA breaks and independent of DNA‐dependent protein kinase.

[1]  J. Kato,et al.  Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae , 1997, Nature.

[2]  M. Lieber,et al.  Interaction of DNA‐dependent protein kinase with DNA and with Ku: biochemical and atomic‐force microscopy studies , 1997, The EMBO journal.

[3]  T. Lindahl,et al.  A newly identified DNA ligase of Saccharomyces cerevisiae involved in RAD52-independent repair of DNA double-strand breaks. , 1997, Genes & development.

[4]  S. Jackson,et al.  Identification of Saccharomyces cerevisiae DNA ligase IV: involvement in DNA double‐strand break repair , 1997, The EMBO journal.

[5]  S. Jackson,et al.  Mammalian DNA double-strand break repair protein XRCC4 interacts with DNA ligase IV , 1997, Current Biology.

[6]  M. Lieber,et al.  Activity of DNA ligase IV stimulated by complex formation with XRCC4 protein in mammalian cells , 1997, Nature.

[7]  D. Ramsden,et al.  Cell-free V(D)J recombination , 1997, Nature.

[8]  M. Lieber,et al.  Yeast DNA ligase IV mediates non-homologous DNA end joining , 1997, Nature.

[9]  Chiyu Wang,et al.  V(D)J recombination in Ku86-deficient mice: distinct effects on coding, signal, and hybrid joint formation. , 1997, Immunity.

[10]  J. Wang,et al.  DNA looping by Ku and the DNA-dependent protein kinase. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[11]  S. Inoue,et al.  Functional interaction between DNA-PK and c-Abl in response to DNA damage , 1997, Nature.

[12]  M. Jung,et al.  Ku proteins join DNA fragments as shown by atomic force microscopy. , 1997, Cancer research.

[13]  D. Lane,et al.  Ku Selectively Transfers between DNA Molecules with Homologous Ends* , 1997, The Journal of Biological Chemistry.

[14]  T. Lindahl,et al.  DNA Ligase IV from HeLa Cell Nuclei* , 1996, The Journal of Biological Chemistry.

[15]  S. Boulton,et al.  Saccharomyces cerevisiae Ku70 potentiates illegitimate DNA double‐strand break repair and serves as a barrier to error‐prone DNA repair pathways. , 1996, The EMBO journal.

[16]  M. Jasin,et al.  Ku80-deficient Cells Exhibit Excess Degradation of Extrachromosomal DNA* , 1996, The Journal of Biological Chemistry.

[17]  M. Hollmann,et al.  A newly identified , 1996 .

[18]  S. Lees-Miller The DNA-dependent protein kinase, DNA-PK: 10 years and no ends in sight. , 1996, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[19]  D. Chan,et al.  Purification and characterization of the double-stranded DNA-activated protein kinase, DNA-PK, from human placenta. , 1996, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[20]  F. Alt,et al.  The XRCC4 gene encodes a novel protein involved in DNA double-strand break repair and V(D)J recombination , 1995, Cell.

[21]  P. Jeggo,et al.  Menage á trois: Double strand break repair, V(D)J recombination and DNA‐PK , 1995, BioEssays : news and reviews in molecular, cellular and developmental biology.

[22]  D. Weaver,et al.  What to do at an end: DNA double-strand-break repair. , 1995, Trends in genetics : TIG.

[23]  P. Jeggo,et al.  Nomenclature of human genes involved in ionizing radiation sensitivity. , 1995, Mutation research.

[24]  D. Ramsden,et al.  Initiation of V(D)J recombination in a cell-free system , 1995, Cell.

[25]  D. Barnes,et al.  Molecular cloning and expression of human cDNAs encoding a novel DNA ligase IV and DNA ligase III, an enzyme active in DNA repair and recombination , 1995, Molecular and cellular biology.

[26]  T. Lindahl,et al.  Repair and Recombination: How to make ends meet , 1995, Current Biology.

[27]  A. Tomkinson,et al.  Mammalian DNA ligase II is highly homologous with vaccinia DNA ligase. Identification of the DNA ligase II active site for enzyme-adenylate formation. , 1994, The Journal of biological chemistry.

[28]  P. Tucker,et al.  Production and characterization of recombinant human Ku antigen. , 1994, Nucleic acids research.

[29]  S. Thode,et al.  Mechanisms of overlap formation in nonhomologous DNA end joining , 1994, Molecular and cellular biology.

[30]  M. Lieber,et al.  V(D)J recombination in mammalian cell mutants defective in DNA double-strand break repair , 1993, Molecular and cellular biology.

[31]  M. Falzon,et al.  EBP-80, a transcription factor closely resembling the human autoantigen Ku, recognizes single- to double-strand transitions in DNA. , 1993, The Journal of biological chemistry.

[32]  F. Alt,et al.  Impairment of V(D)J recombination in double-strand break repair mutants. , 1993, Science.

[33]  S. Jackson,et al.  The DNA-dependent protein kinase: Requirement for DNA ends and association with Ku antigen , 1993, Cell.

[34]  A. Montecucco,et al.  Rat liver DNA ligases. Catalytic properties of a novel form of DNA ligase. , 1992, European journal of biochemistry.

[35]  T. Lindahl,et al.  Mammalian DNA ligases. , 1992, Annual review of biochemistry.

[36]  F. Strauss,et al.  Analysis of the mechanism of interaction of simian Ku protein with DNA. , 1991, Nucleic acids research.

[37]  P. Jeggo,et al.  Studies on mammalian mutants defective in rejoining double-strand breaks in DNA. , 1990, Mutation research.

[38]  A. Arnberg,et al.  HeLa nuclear protein recognizing DNA termini and translocating on DNA forming a regular DNA-multimeric protein complex. , 1989, Journal of molecular biology.

[39]  D. Roth,et al.  Mechanisms of nonhomologous recombination in mammalian cells , 1985, Molecular and cellular biology.