Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
Mol Cell. 2010 Dec 22;40(6):988-1000. doi: 10.1016/j.molcel.2010.11.016.
Holliday junction (HJ) resolution is required for segregation of chromosomes and for formation of crossovers during homologous recombination. The identity of the resolvase(s) that functions in vivo has yet to be established, although several proteins able to cut HJs in vitro have been identified as candidates in yeasts and mammals. Using an assay to detect unselected products of mitotic recombination, we found a significant decrease in crossovers in the Saccharomyces cerevisiae mus81Δ mutant. Yen1 serves a backup function responsible for resolving intermediates in mus81Δ mutants, or when conversion tracts are short. In the absence of both Mus81 and Yen1, intermediates are not channeled exclusively to noncrossover recombinants, but instead are processed by Pol32-dependent break-induced replication (BIR). The channeling of recombination from reciprocal exchange to BIR results in greatly increased spontaneous loss of heterozygosity (LOH) and chromosome mis-segregation in the mus81Δ yen1Δ mutant, typical of the genomic instability found in tumor cells.
霍利迪连接（HJ）的解决是为了在染色体分离和同源重组过程中形成交叉。虽然已经鉴定出几种能够在体外切割 HJ 的蛋白质作为酵母和哺乳动物中的候选物，但在体内起作用的解旋酶的身份尚未确定。使用一种检测有丝分裂重组未选择产物的测定法，我们发现酿酒酵母 mus81Δ 突变体中的交叉明显减少。 Yen1 作为备份功能，负责解决 mus81Δ 突变体中的中间体，或当转换片段较短时。在没有 Mus81 和 Yen1 的情况下，中间体不会专门流向非交叉重组体，而是通过 Pol32 依赖性断裂诱导复制（BIR）进行处理。从交互交换到 BIR 的重组通道会导致 mus81Δ yen1Δ 突变体中自发杂合性丢失（LOH）和染色体错误分离大大增加，这是肿瘤细胞中发现的基因组不稳定性的典型特征。
