Chernenkov A Iu, Fedorov D V, Gracheva L M, Evstukhina T A, Koval'tsova S V, Peshekhonov V T, Fedorova I V, Korolev V G
Genetika. 2012 Mar;48(3):333-9.
It was assumed previously that the mutator phenotype of the hms3 mutant was determined by processes taking place in the D-loop. As a next step, genetic analysis was performed to study the interactions between the hsm3 mutation and mutations of the genes that control the initial steps of the D-loop formation. The mutations of the MMS4 and XRS2 genes, which initiate the double-strand break formation and subsequent repair, were shown to completely block HSM3-dependent UV-induced mutagenesis. Mutations of the RAD51, RAD52, and RAD54 genes, which are also involved in the D-loop formation, only slightly decreased the level of UV-induced mutagenesis in the hsm3 mutant. Similar results were observed for the interaction of hsm3 with the mph1 mutation, which stabilizes the D-loop. In contrast, the shu1 mutation, which destabilizes the D-loop structure, led to an extremely high level of UV-induced mutagenesis and displayed epistatic interactions with the hsm3 mutation. The results made it possible to assume that the hsm3 mutation destabilizes the D-loop, which is a key substrate of both Rad5- and Rad52-dependent postreplicative repair pathways.
先前假定hms3突变体的突变体表型是由D环中发生的过程所决定的。作为下一步，进行了遗传分析以研究hsm3突变与控制D环形成初始步骤的基因的突变之间的相互作用。启动双链断裂形成及后续修复的MMS4和XRS2基因的突变被证明可完全阻断HSM3依赖的紫外线诱导的诱变。同样参与D环形成的RAD51、RAD52和RAD54基因的突变仅略微降低了hsm3突变体中紫外线诱导的诱变水平。对于hsm3与稳定D环的mph1突变的相互作用也观察到了类似结果。相反，使D环结构不稳定的shu1突变导致了极高水平的紫外线诱导的诱变，并与hsm3突变表现出上位性相互作用。这些结果使得可以假定hsm3突变使D环不稳定，而D环是Rad5和Rad52依赖的复制后修复途径的关键底物。
