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Mol Cell. 2013 Oct 24;52(2):221-33. doi: 10.1016/j.molcel.2013.08.036. Epub 2013 Sep 26.

Cooperative control of holliday junction resolution and DNA repair by the SLX1 and MUS81-EME1 nucleases.

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1
MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.

Abstract

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.

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PMID:
24076219
PMCID:
PMC3808987
DOI:
10.1016/j.molcel.2013.08.036
[Indexed for MEDLINE]
Free PMC Article
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