Signon L, Malkova A, Naylor M L, Klein H, Haber J E
Department of Biology and Rosenstiel Center, Brandeis University, Waltham, Massachusetts 02254-9110, USA.
Mol Cell Biol. 2001 Mar;21(6):2048-56. doi: 10.1128/MCB.21.6.2048-2056.2001.
Broken chromosomes can be repaired by several homologous recombination mechanisms, including gene conversion and break-induced replication (BIR). In Saccharomyces cerevisiae, an HO endonuclease-induced double-strand break (DSB) is normally repaired by gene conversion. Previously, we have shown that in the absence of RAD52, repair is nearly absent and diploid cells lose the broken chromosome; however, in cells lacking RAD51, gene conversion is absent but cells can repair the DSB by BIR. We now report that gene conversion is also abolished when RAD54, RAD55, and RAD57 are deleted but BIR occurs, as with rad51Delta cells. DSB-induced gene conversion is not significantly affected when RAD50, RAD59, TID1 (RDH54), SRS2, or SGS1 is deleted. Various double mutations largely eliminate both gene conversion and BIR, including rad51Delta rad50Delta, rad51Delta rad59Delta, and rad54Delta tid1Delta. These results demonstrate that there is a RAD51- and RAD54-independent BIR pathway that requires RAD59, TID1, RAD50, and presumably MRE11 and XRS2. The similar genetic requirements for BIR and telomere maintenance in the absence of telomerase also suggest that these two processes proceed by similar mechanisms.
断裂的染色体可通过几种同源重组机制进行修复，包括基因转换和断裂诱导复制（BIR）。在酿酒酵母中，HO核酸内切酶诱导的双链断裂（DSB）通常通过基因转换进行修复。此前，我们已经表明，在缺乏RAD52的情况下，修复几乎不存在，二倍体细胞会丢失断裂的染色体；然而，在缺乏RAD51的细胞中，基因转换不存在，但细胞可以通过BIR修复DSB。我们现在报告，当RAD54、RAD55和RAD57缺失时，基因转换也会被消除，但BIR会发生，就像rad51Delta细胞一样。当RAD50、RAD59、TID1（RDH54）、SRS2或SGS1缺失时，DSB诱导的基因转换没有受到显著影响。各种双突变在很大程度上消除了基因转换和BIR，包括rad51Delta rad50Delta、rad51Delta rad59Delta和rad54Delta tid1Delta。这些结果表明，存在一条不依赖RAD51和RAD54的BIR途径，该途径需要RAD59、TID1、RAD50，可能还需要MRE11和XRS2。在没有端粒酶的情况下，BIR和端粒维持对遗传的相似需求也表明这两个过程通过相似的机制进行。
