Oh Steve D, Lao Jessica P, Hwang Patty Yi-Hwa, Taylor Andrew F, Smith Gerald R, Hunter Neil
Section of Microbiology, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
Cell. 2007 Jul 27;130(2):259-72. doi: 10.1016/j.cell.2007.05.035.
Bloom's helicase (BLM) is thought to prevent crossing-over during DNA double-strand-break repair (DSBR) by disassembling double-Holliday junctions (dHJs) or by preventing their formation. We show that the Saccharomyces cerevisiae BLM ortholog, Sgs1, prevents aberrant crossing-over during meiosis by suppressing formation of joint molecules (JMs) comprising three and four interconnected duplexes. Sgs1 and procrossover factors, Msh5 and Mlh3, are antagonistic since Sgs1 prevents dHJ formation in msh5 cells and sgs1 mutation alleviates crossover defects of both msh5 and mlh3 mutants. We propose that differential activity of Sgs1 and procrossover factors at the two DSB ends effects productive formation of dHJs and crossovers and prevents multichromatid JMs and counterproductive crossing-over. Strand invasion of different templates by both DSB ends may be a common feature of DSBR that increases repair efficiency but also the likelihood of associated crossing-over. Thus, by disrupting aberrant JMs, BLM-related helicases maximize repair efficiency while minimizing the risk of deleterious crossing-over.
布鲁姆解旋酶（BLM）被认为通过拆解双霍利迪连接体（dHJs）或阻止其形成，来防止DNA双链断裂修复（DSBR）过程中的交叉互换。我们发现，酿酒酵母中的BLM直系同源物Sgs1，通过抑制由三个和四个相互连接的双链体组成的联合分子（JMs）的形成，来防止减数分裂过程中的异常交叉互换。Sgs1与促进交叉互换的因子Msh5和Mlh3相互拮抗，因为Sgs1可防止msh5细胞中dHJ的形成，而sgs1突变可减轻msh5和mlh3突变体的交叉互换缺陷。我们提出，Sgs1和促进交叉互换因子在两个双链断裂末端的不同活性，影响了dHJ和交叉互换的有效形成，并防止了多染色单体JMs和适得其反的交叉互换。两个双链断裂末端对不同模板的链入侵，可能是DSBR的一个共同特征，这增加了修复效率，但也增加了相关交叉互换的可能性。因此，通过破坏异常JMs，与BLM相关的解旋酶在将有害交叉互换风险降至最低的同时，使修复效率最大化。
