Together, DNA repair and checkpoint responses ensure the integrity of the genome. Coordination of cell cycle checkpoints and DNA repair are especially important following genotoxic radiation or chemotherapy, during which unusually high loads of DNA damage are sustained.
MUS81 encodes a helix-hairpin-helix protein involved in the response to USLV and methylation-induced DNA damage in Saccharomyces cerevisiae (1). Mus81 is important for replicational stress tolerance in both budding and fission yeast.
Specifically, Mus81 associates with Eme1 to form an endonuclease that can process stalled replication forks before they have regressed to form a Holliday junction.
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.
Mus81 is involved in the recruitment of Cds1 to aberrant DNA structures where Cds1 modulates the activity of damage tolerance enzymes. The gene encoding human MUS81 maps to chromosome 11q13 and encodes a 551 amino acid protein.
Function:
Interacts with EME1 and EME2 to form a DNA structure-specific endonuclease with substrate preference for branched DNA structures with a 5'-end at the branch nick. Typical substrates include 3'-flap structures, replication forks and nicked Holliday junctions. May be required in mitosis for the processing of stalled or collapsed replication forks.
Subcellular Location:
Nucleus; nucleolus. Recruited to foci of DNA damage in S-phase cells.
Tissue Specificity:
Widely expressed.
Similarity:
Belongs to the XPF family.
Contains 1 ERCC4 domain.
SWISS:
Q96NY9
Gene ID:
80198
Database links:
Entrez Gene: 80198 Human
Entrez Gene: 71711 Mouse
Entrez Gene: 293678 Rat
Omim: 606591 Human
SwissProt: Q1JPC1 Cow
SwissProt: Q2KIT9 Cow
SwissProt: Q96NY9 Human
SwissProt: Q91ZJ0 Mouse
SwissProt: Q4KM32 Rat
Unigene: 288798 Human
Unigene: 27697 Mouse
Unigene: 137652 Rat
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