Cooperative Control of Holliday Junction Resolution and DNA Repair by the SLX1 and MUS81-EME1 Nucleases

被引：123

作者：

Castor, Dennis ^{[1
]}

Nair, Nidhi ^{[1
]}

Declais, Anne-Cecile ^{[2
]}

Lachaud, Christophe ^{[1
]}

Toth, Rachel ^{[1
]}

Macartney, Thomas J. ^{[1
]}

Lilley, David M. J. ^{[2
]}

Arthur, J. Simon C. ^{[3
]}

Rouse, John ^{[1
]}

机构：

[1] Univ Dundee, Coll Life Sci, MRC, Prot Phosphorylat & Ubiquitylat Unit, Dundee DD1 5EH, Scotland

[2] Univ Dundee, Coll Life Sci, CR UK Nucle Acid Struct Res Grp, Dundee DD1 5EH, Scotland

[3] Univ Dundee, Coll Life Sci, Div Cell Signalling & Immunol, Dundee DD1 5EH, Scotland

来源：

MOLECULAR CELL | 2013年 / 52卷 / 02期

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会; 英国工程与自然科学研究理事会;

关键词：

STRUCTURE-SPECIFIC ENDONUCLEASES; FANCONI-ANEMIA; DROSOPHILA MUS312; IDENTIFICATION; RECOMBINATION; INVOLVEMENT; DISRUPTION; RESOLVASE;

D O I：

10.1016/j.molcel.2013.08.036

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：221 / 233

页数：13

共 43 条

[1]

Combinatorial Regulation of Meiotic Holliday Junction Resolution in C. elegans by HIM-6 (BLM) Helicase, SLX-4, and the SLX-1, MUS-81 and XPF-1 Nucleases [J].