Cooperative control of holliday junction resolution and DNA repair by the SLX1 and MUS81-EME1 nucleases.
Cooperative control of holliday junction resolution and DNA repair by the SLX1 and MUS81-EME1 nucleases.
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SLX1和MUS81-EME1核酸酶对Holliday连接分辨率和DNA修复的合作控制。
DOI：
10.1016/j.molcel.2013.08.036
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发表时间：
2013-10-24
期刊：
影响因子：
16
通讯作者：
Rouse, John
中科院分区：
文献类型：
--
作者：
Castor, Dennis;Nair, Nidhi;Declais, Anne-Cecile;Lachaud, Christophe;Toth, Rachel;Macartney, Thomas J.;Lilley, David M. J.;Arthur, J. Simon C.;Rouse, John
霍利迪连接（HJs）是同源重组过程中出现的X形DNA结构，必须将其去除以实现染色体分离。SLX 1和MUS 81-EME 1核酸酶都可以在体外处理HJ，并且它们在SLX 4支架上紧密结合，暗示可能的合作。然而，哺乳动物SLX 1的细胞作用尚不清楚。在这里，我们使用小鼠遗传学和结构功能分析来研究SLX 1的功能。破坏小鼠Slx 1和Slx 4基因揭示了它们对于有丝分裂细胞中的HJ分辨率是必不可少的。此外，SLX 1和MUS 81-EME 1共同作用，以需要绑定到SLX 4的方式解析HJ。我们还表明，SLX 1，像MUS 81-EME 1，需要修复DNA链间交联，但这种作用似乎是独立的HJ切割，至少在小鼠细胞。这些发现阐明了哺乳动物中的HJ分辨率和基因组稳定性的维持。小鼠细胞中Holliday连接的分解需要SLX 1核酸酶SLX 1在HJ分解和ICL修复中与MUS 81-EME 1协同作用。SLX 4中阻止其与SLX 1和MUS 81-EME 1结合的突变消除HJ分解。
Holliday junctions (HJs) are X-shaped DNA structures that arise during homologous recombination, which must be removed to enable chromosome segregation. The SLX1 and MUS81-EME1 nucleases can both process HJs in vitro, and they bind in close proximity on the SLX4 scaffold, hinting at possible cooperation. However, the cellular roles of mammalian SLX1 are not yet known. Here, we use mouse genetics and structure function analysis to investigate SLX1 function. Disrupting the murine Slx1 and Slx4 genes revealed that they are essential for HJ resolution in mitotic cells. Moreover, SLX1 and MUS81-EME1 act together to resolve HJs in a manner that requires tethering to SLX4. We also show that SLX1, like MUS81-EME1, is required for repair of DNA interstrand crosslinks, but this role appears to be independent of HJ cleavage, at least in mouse cells. These findings shed light on HJ resolution in mammals and on maintenance of genome stability. Resolution of Holliday junctions in mouse cells requires the SLX1 nuclease SLX1 acts cooperatively with MUS81-EME1 in HJ resolution and ICL repair Mutations in SLX4 that prevent it binding to SLX1 and MUS81-EME1 abolish HJ resolution DNA substrates of SLX1 and MUS81-EME1 in ICL repair appear to be different from HJs
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影响因子：
4.5
作者：
Holloway JK;Booth J;Edelmann W;McGowan CH;Cohen PE
通讯作者：
Cohen PE
影响因子：
4.5
作者：
Bailly AP;Freeman A;Hall J;Déclais AC;Alpi A;Lilley DM;Ahmed S;Gartner A
通讯作者：
Gartner A
影响因子：
4.5
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Agostinho A;Meier B;Sonneville R;Jagut M;Woglar A;Blow J;Jantsch V;Gartner A
通讯作者：
Gartner A
影响因子：
4.5
作者：
Holloway JK;Mohan S;Balmus G;Sun X;Modzelewski A;Borst PL;Freire R;Weiss RS;Cohen PE
通讯作者：
Cohen PE
影响因子：
30.8
作者：
Kim, Yonghwan;Lach, Francis P.;Desetty, Rohini;Hanenberg, Helmut;Auerbach, Arleen D.;Smogorzewska, Agata
通讯作者：
Smogorzewska, Agata