Mms22p protects Saccharomyces cerevisiae from DNA damage induced by topoisomerase II.
Mms22p protects Saccharomyces cerevisiae from DNA damage induced by topoisomerase II.
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DOI：
10.1093/nar/gki246
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发表时间：
2005
影响因子：
14.9
通讯作者：
Osheroff N
中科院分区：
文献类型：
--
作者：
Baldwin EL;Berger AC;Corbett AH;Osheroff N
拓扑异构酶II的切割反应产生双链DNA断裂，在癌症的治愈和引发中起着核心作用。因此，重要的是要了解修复拓扑异构酶II产生的DNA损伤的细胞过程。使用酿酒酵母的全基因组方法，我们发现Δ mre 11，Δ xrs 2，Δ rad 50，Δ rad 51，Δ rad 52，Δ rad 54，Δ rad 55，Δ rad 57和Δ mms 22菌株对依托泊苷过敏，依托泊苷是一种特异性增加拓扑异构酶II介导的DNA断裂水平的药物。这些结果证实了同源重组的单链侵入途径是修复拓扑异构酶II诱导的酵母DNA损伤的主要途径，也表明Mms 22 p的重要作用。虽然Δ mms 22菌株对几种DNA损伤剂敏感，但对Mms 22 p的功能知之甚少。Δ mms 22培养物在G2/M期积累，并显示对拓扑异构酶II介导的DNA损伤的异常细胞周期反应。MMS 22似乎在单链侵袭途径之外发挥作用，但在Δ MMS 22细胞中依托泊苷诱导的同源重组水平低于野生型。MMS 22与RTT 101和RTT 107是上位性的，RTT 101和RTT 107是编码其蛋白结合伴侣的基因。最后，与在DNA过程中的作用一致，Mms 22 p定位于离散的核灶，即使在没有依托泊苷或其结合伙伴的情况下。
The cleavage reaction of topoisomerase II, which creates double-stranded DNA breaks, plays a central role in both the cure and initiation of cancer. Therefore, it is important to understand the cellular processes that repair topoisomerase II-generated DNA damage. Using a genome-wide approach with Saccharomyces cerevisiae, we found that Δmre11, Δxrs2, Δrad50, Δrad51, Δrad52, Δrad54, Δrad55, Δrad57 and Δmms22 strains were hypersensitive to etoposide, a drug that specifically increases levels of topoisomerase II-mediated DNA breaks. These results confirm that the single-strand invasion pathway of homologous recombination is the major pathway that repairs topoisomerase II-induced DNA damage in yeast and also indicate an important role for Mms22p. Although Δmms22 strains are sensitive to several DNA-damaging agents, little is known about the function of Mms22p. Δmms22 cultures accumulate in G2/M, and display an abnormal cell cycle response to topoisomerase II-mediated DNA damage. MMS22 appears to function outside of the single-strand invasion pathway, but levels of etoposide-induced homologous recombination in Δmms22 cells are lower than wild-type. MMS22 is epistatic with RTT101 and RTT107, genes that encode its protein binding partners. Finally, consistent with a role in DNA processes, Mms22p localizes to discrete nuclear foci, even in the absence of etoposide or its binding partners.
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影响因子：
2.9
作者：
Byl, JAW;Cline, SD;Osheroff, N
通讯作者：
Osheroff, N
影响因子：
30.8
作者：
Bennett, CB;Lewis, LK;Resnick, MA
通讯作者：
Resnick, MA
影响因子：
64.8
作者：
Berger, JM;Gamblin, SJ;Wang, JC
通讯作者：
Wang, JC
影响因子：
64.8
作者：
Friedberg, EC
通讯作者：
Friedberg, EC
影响因子：
2.1
作者：
Araki, Y;Kawasaki, Y;Sugino, A
通讯作者：
Sugino, A