| Literature DB >> 19596236 |
Samira Fekairi1, Sarah Scaglione, Charly Chahwan, Ewan R Taylor, Agnès Tissier, Stéphane Coulon, Meng-Qiu Dong, Cristian Ruse, John R Yates, Paul Russell, Robert P Fuchs, Clare H McGowan, Pierre-Henri L Gaillard.
Abstract
Structure-specific endonucleases resolve DNA secondary structures generated during DNA repair and recombination. The yeast 5' flap endonuclease Slx1-Slx4 has received particular attention with the finding that Slx4 has Slx1-independent key functions in genome maintenance. Although Slx1 is a highly conserved protein in eukaryotes, no orthologs of Slx4 were reported other than in fungi. Here we report the identification of Slx4 orthologs in metazoa, including fly MUS312, essential for meiotic recombination, and human BTBD12, an ATM/ATR checkpoint kinase substrate. Human SLX1-SLX4 displays robust Holliday junction resolvase activity in addition to 5' flap endonuclease activity. Depletion of SLX1 and SLX4 results in 53BP1 foci accumulation and H2AX phosphorylation as well as cellular hypersensitivity to MMS. Furthermore, we show that SLX4 binds the XPF(ERCC4) and MUS81 subunits of the XPF-ERCC1 and MUS81-EME1 endonucleases and is required for DNA interstrand crosslink repair. We propose that SLX4 acts as a docking platform for multiple structure-specific endonucleases.Entities:
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Year: 2009 PMID： 19596236 PMCID： PMC2861413 DOI： 10.1016/j.cell.2009.06.029
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582