Human Mus81-associated endonuclease cleaves Holliday junctions in vitro

Mol Cell. 2001 Nov;8(5):1117-27. doi: 10.1016/s1097-2765(01)00375-6.


Mus81, a protein with homology to the XPF subunit of the ERCC1-XPF endonuclease, is important for replicational stress tolerance in both budding and fission yeast. Human Mus81 has associated endonuclease activity against structure-specific oligonucleotide substrates, including synthetic Holliday junctions. Mus81-associated endonuclease resolves Holliday junctions into linear duplexes by cutting across the junction exclusively on strands of like polarity. In addition, Mus81 protein abundance increases in cells following exposure to agents that block DNA replication. Taken together, these findings suggest a role for Mus81 in resolving Holliday junctions that arise when DNA replication is blocked by damage or by nucleotide depletion. Mus81 is not related by sequence to previously characterized Holliday junction resolving enzymes, and it has distinct enzymatic properties that suggest it uses a novel enzymatic strategy to cleave Holliday junctions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cloning, Molecular
  • DNA / metabolism*
  • DNA Damage
  • DNA Replication / physiology*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Endonucleases*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Humans
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nucleic Acid Conformation
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae Proteins
  • Sequence Alignment


  • DNA-Binding Proteins
  • Fungal Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • DNA
  • Endonucleases
  • MUS81 protein, S cerevisiae
  • MUS81 protein, human

Associated data

  • GENBANK/AF425646
  • GENBANK/AF425647