Identification of a DNA nonhomologous end-joining complex in bacteria.
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.
Weller
Geoffrey R
GR
Cambridge Institute for Medical Research & Department of Haematology, University of Cambridge, Hills Road, Cambridge CB2 2XY, UK.
Kysela
Boris
B
Roy
Rajat
R
Tonkin
Louise M
LM
Scanlan
Elizabeth
E
Della
Marina
M
Devine
Susanne Krogh
SK
Day
Jonathan P
JP
Wilkinson
Adam
A
d'Adda di Fagagna
Fabrizio
F
Devine
Kevin M
KM
Bowater
Richard P
RP
Jeggo
Penny A
PA
Jackson
Stephen P
SP
Doherty
Aidan J
AJ
D034961:Antigens, Nuclear; D001412:Bacillus subtilis / Q000235:genetics*; D001426:Bacterial Proteins / Q000378:metabolism; D001665:Binding Sites; D004249:DNA Damage; D004265:DNA Helicases; D011088:DNA Ligases / Q000378:metabolism*; D004260:DNA Repair; D004269:DNA, Bacterial / Q000096:biosynthesis* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D000072200:Ku Autoantigen; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding
D034961:Antigens, Nuclear; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C101467:XRCC4 protein, human; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; D011088:DNA Ligases