A winged helix domain in human MUS81 binds DNA and modulates the endonuclease activity of MUS81 complexes

نویسندگان

  • Andrew J. Fadden
  • Stephanie Schalbetter
  • Maureen Bowles
  • Richard Harris
  • John Lally
  • Antony M. Carr
  • Neil Q. McDonald
چکیده

The MUS81-EME1 endonuclease maintains metazoan genomic integrity by cleaving branched DNA structures that arise during the resolution of recombination intermediates. In humans, MUS81 also forms a poorly characterized complex with EME2. Here, we identify and determine the structure of a winged helix (WH) domain from human MUS81, which binds DNA. WH domain mutations greatly reduce binding of the isolated domain to DNA and impact on incision activity of MUS81-EME1/EME2 complexes. Deletion of the WH domain reduces the endonuclease activity of both MUS81-EME1 and MUS81-EME2 complexes, and incisions made by MUS81-EME2 are made closer to the junction on substrates containing a downstream duplex, such as fork structures and nicked Holliday junctions. WH domain mutation or deletion in Schizosaccharomyces pombe phenocopies the DNA-damage sensitivity of strains deleted for mus81. Our results indicate an important role for the WH domain in both yeast and human MUS81 complexes.

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عنوان ژورنال:

دوره 41  شماره 

صفحات  -

تاریخ انتشار 2013