Identification of a DNA nonhomologous end-joining complex in bacteria

被引:252
作者
Weller, GR
Kysela, B
Roy, R
Tonkin, LM
Scanlan, E
Della, M
Devine, SK
Day, JP
Wilkinson, A
di Fagagna, FD
Devine, KM
Bowater, RP
Jeggo, PA
Jackson, SP
Doherty, AJ
机构
[1] Univ Cambridge, Cambridge Inst Med Res, Cambridge CB2 2XY, England
[2] Univ Cambridge, Dept Haematol, Cambridge CB2 2XY, England
[3] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England
[4] Univ Cambridge, Dept Zool, Cambridge CB2 1QR, England
[5] Univ Cambridge, Wellcome Trust Canc Res UK, Inst Canc & Dev Biol, Cambridge CB2 1QR, England
[6] Univ Dublin Trinity Coll, Smurfit Inst, Dept Genet, Dublin 2, Ireland
[7] Univ E Anglia, Sch Biol Sci, Norwich NR4 7TJ, Norfolk, England
关键词
D O I
10.1126/science.1074584
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
in eukaryotic cells, double-strand breaks (DSBs) in DNA are generally repaired by the pathway of homologous recombination or by DNA nonhomologous end joining (NHEJ). Both pathways have been highly conserved throughout eukaryotic evolution, but no equivalent NHEJ system has been identified in prokaryotes. The NHEJ pathway requires a DNA end-binding component called Ku. We have identified bacterial Ku homologs and show that these proteins retain the biochemical characteristics of the eukaryotic Ku heterodimer. Furthermore, we show that bacterial Ku specifically recruits DNA ligase to DNA ends and stimulates DNA ligation. Loss of these proteins leads to hypersensitivity to ionizing radiation in Bacillus subtilis. These data provide evidence that many bacteria possess a DNA DSB repair apparatus that shares many features with the NHEJ system of eukarya and suggest that this DNA repair pathway arose before the prokaryotic and eukaryotic lineages diverged.
引用
收藏
页码:1686 / 1689
页数:4
相关论文
共 34 条
  • [1] Prokaryotic homologs of the eukaryotic DNA-end-binding protein Ku, novel domains in the Ku protein and prediction of a prokaryotic double-strand break repair system
    Aravind, L
    Koonin, EV
    [J]. GENOME RESEARCH, 2001, 11 (08) : 1365 - 1374
  • [2] Ku selectively transfers between DNA molecules with homologous ends
    Bliss, TM
    Lane, DP
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (09) : 5765 - 5773
  • [3] DNA looping by Ku and the DNA-dependent protein kinase
    Cary, RB
    Peterson, SR
    Wang, JT
    Bear, DG
    Bradbury, EM
    Chen, DJ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (09) : 4267 - 4272
  • [4] Interactions of the DNA ligase IV-XRCC4 complex with DNA ends and the DNA-dependent protein kinase
    Chen, L
    Trujillo, K
    Sung, P
    Tomkinson, AE
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (34) : 26196 - 26205
  • [5] DNA-end-joining: from yeast to man
    Critchlow, SE
    Jackson, SP
    [J]. TRENDS IN BIOCHEMICAL SCIENCES, 1998, 23 (10) : 394 - 398
  • [6] Conservation of gene order: a fingerprint of proteins that physically interact
    Dandekar, T
    Snel, B
    Huynen, M
    Bork, P
    [J]. TRENDS IN BIOCHEMICAL SCIENCES, 1998, 23 (09) : 324 - 328
  • [7] DIFAGAGNA FD, UNPUB
  • [8] Structural and mechanistic conservation in DNA ligases
    Doherty, AJ
    Suh, SW
    [J]. NUCLEIC ACIDS RESEARCH, 2000, 28 (21) : 4051 - 4058
  • [9] DNA repair: How Ku makes ends meet
    Doherty, AJ
    Jackson, SR
    [J]. CURRENT BIOLOGY, 2001, 11 (22) : R920 - R924
  • [10] Identification of bacterial homologues of the Ku DNA repair proteins
    Doherty, AJ
    Jackson, SP
    Weller, GR
    [J]. FEBS LETTERS, 2001, 500 (03) : 186 - 188