Weller Geoffrey R, Kysela Boris, Roy Rajat, Tonkin Louise M, Scanlan Elizabeth, Della Marina, Devine Susanne Krogh, Day Jonathan P, Wilkinson Adam, d'Adda di Fagagna Fabrizio, Devine Kevin M, Bowater Richard P, Jeggo Penny A, Jackson Stephen P, Doherty Aidan J
Cambridge Institute for Medical Research & Department of Haematology, University of Cambridge, Hills Road, Cambridge CB2 2XY, UK.
Science. 2002 Sep 6;297(5587):1686-9. doi: 10.1126/science.1074584.
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.
在真核细胞中,DNA双链断裂(DSB)通常通过同源重组途径或DNA非同源末端连接(NHEJ)进行修复。这两种途径在整个真核生物进化过程中都高度保守,但在原核生物中尚未发现等效的NHEJ系统。NHEJ途径需要一种称为Ku的DNA末端结合成分。我们已经鉴定出细菌Ku同源物,并表明这些蛋白质保留了真核Ku异二聚体的生化特性。此外,我们表明细菌Ku特异性地将DNA连接酶募集到DNA末端并刺激DNA连接。这些蛋白质的缺失导致枯草芽孢杆菌对电离辐射高度敏感。这些数据提供了证据,表明许多细菌拥有一种与真核生物NHEJ系统具有许多共同特征的DNA DSB修复装置,并表明这种DNA修复途径在原核生物和真核生物谱系分化之前就已出现。