REPAIRtoire - a database of DNA repair pathways

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Protein FULL name:

Crossover junction endonuclease MUS81, MMS and UV-sensitive protein 81

Mus81p (Saccharomyces cerevisiae) is product of expression of MUS81 gene.

Mus81p is involved in:

HRR in Saccharomyces cerevisiae


FUNCTION: Interacts with MMS4 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, D-loops, replication forks with regressed leading strands and nicked Holliday junctions. Cleavage probably occurs approximately half a helical turn upstream of the free 5'-end in these structures. May be required in mitosis for the processing of stalled replication fork intermediates arising spontaneously or subsequent to treatment with DNA damaging agents such as methylmethane sulfonate (MMS), camptothecin (CPT) or UV. May be required in meiosis for the repair of meiosis-specific double strand breaks subsequent to single-end invasion (SEI). This involves consecutive cleavage of D-loops and nicked Holliday junctions leading to sister chromatid crossover. In contrast to MSH4-MSH5 dependent crossover, double Holliday junctions do not seem to be involved. Spore formation and viability are severely impaired in deletion strains.

COFACTOR: Magnesium or manganese.

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=31.1 nM for a nicked Holliday junction; KM=6.84 nM for a regressed leading strand replication fork; KM=4.8 nM for for a 3'-flap structure; KM=3.45 nM for a nicked duplex; KM=14.0 nM for a regressed lagging strand replication fork; KM=245 nM for a Y structure; KM=173 nM for a double flap structure; Vmax=55.6 nmol/min/ng enzyme with a nicked Holliday junction as substrate; Vmax=31.3 nmol/min/ng enzyme with a regressed leading strand replication fork as substrate; Vmax=24.4 nmol/min/ng enzyme with a 3'-flap structure as substrate; Vmax=2.21 nmol/min/ng enzyme with a nicked duplex as substrate; Vmax=0.832 nmol/min/ng enzyme with a regressed lagging strand replication fork as subsystrate; Vmax=0.0468 nmol/min/ng enzyme with a Y structure as substrate; Vmax=0.0879 nmol/min/ng enzyme with a double flap structure as substrate; pH dependence: Optimum pH is 8.0 for the cleavage of a 3'-flap structure;

SUBUNIT: Interacts with MMS4 and RAD54.

INTERACTION: P38257:MMS4; NbExp=1; IntAct=EBI-33508, EBI-21547;


MISCELLANEOUS: Two distinct classes of meiotic crossovers have been demonstrated in budding yeast. Class I crossovers exhibit crossover interference and require MSH4 and MSH5 for their resolution, while class II crossovers exhibit no crossover interference and require MUS81 and MMS4. While class I crossovers represent the majority of crossovers in S.cerevisiae, they are virtually absent in S.pombe, which lacks orthologs of MSH4 and MSH5.

MISCELLANEOUS: Present with 300 molecules/cell in log phase SD medium.

SIMILARITY: Belongs to the XPF family.

SIMILARITY: Contains 1 ERCC4 domain.

NCBI GenPept GI number(s): 46396280
Species: Saccharomyces cerevisiae

Links to other databases:

Database ID Link
Uniprot Q04149 Q04149
PFAM: PF02732
InterPro: IPR010996
CATH: - -
SCOP: - -
PDB: - -

Protein sequence:

Mus81p (Saccharomyces cerevisiae) is able to recognize following damages:
Mus81p (Saccharomyces cerevisiae) belongs to following protein families:

Title Authors Journal
The nucleotide sequence of Saccharomyces cerevisiae chromosome IV. Jacq C, Alt-Morbe J, Andre B, Arnold W, Bahr A, Ballesta JP, Bargues M, Baron L, Becker A, Biteau N, Blocker H, Blugeon C, Boskovic J, Brandt P, Bruckner M, Buitrago MJ, Coster F, Delaveau T, del Rey F, Dujon B, Eide LG, Garcia-Cantalejo JM, Goffeau A, Gomez-Peris A, Zaccaria P, et al. Nature May 1, 1997
MUS81 encodes a novel helix-hairpin-helix protein involved in the response to UV- and methylation-induced DNA damage in Saccharomyces cerevisiae. Interthal H, Heyer WD Mol Gen Genet June 1, 2000
Requirement for three novel protein complexes in the absence of the Sgs1 DNA helicase in Saccharomyces cerevisiae. Mullen JR, Kaliraman V, Ibrahim SS, Brill SJ Genetics Feb. 1, 2001
Functional overlap between Sgs1-Top3 and the Mms4-Mus81 endonuclease. Kaliraman V, Mullen JR, Fricke WM, Bastin-Shanower SA, Brill SJ Genes Dev Oct. 15, 2001
Alternate pathways involving Sgs1/Top3, Mus81/ Mms4, and Srs2 prevent formation of toxic recombination intermediates from single-stranded gaps created by DNA replication. Fabre F, Chan A, Heyer WD, Gangloff S Proc Natl Acad Sci U S A Dec. 24, 2002
Cleavage of model replication forks by fission yeast Mus81-Eme1 and budding yeast Mus81-Mms4. Whitby MC, Osman F, Dixon J J Biol Chem Jan. 28, 2003
The Mus81/Mms4 endonuclease acts independently of double-Holliday junction resolution to promote a distinct subset of crossovers during meiosis in budding yeast. de los Santos T, Hunter N, Lee C, Larkin B, Loidl J, Hollingsworth NM Genetics May 1, 2003
The mechanism of Mus81-Mms4 cleavage site selection distinguishes it from the homologous endonuclease Rad1-Rad10. Bastin-Shanower SA, Fricke WM, Mullen JR, Brill SJ Mol Cell Biol May 1, 2003
Generating crossovers by resolution of nicked Holliday junctions: a role for Mus81-Eme1 in meiosis. Osman F, Dixon J, Doe CL, Whitby MC Mol Cell Sept. 1, 2003
Global analysis of protein expression in yeast. Ghaemmaghami S, Huh WK, Bower K, Howson RW, Belle A, Dephoure N, O'Shea EK, Weissman JS Nature Oct. 16, 2003
Functional domains required for the Saccharomyces cerevisiae Mus81-Mms4 endonuclease complex formation and nuclear localization. Fu Y, Xiao W DNA Repair (Amst) Dec. 9, 2003
The Mus81 solution to resolution: generating meiotic crossovers without Holliday junctions. Hollingsworth NM, Brill SJ Genes Dev Feb. 15, 2004
Substrate specificity of the Saccharomyces cerevisiae Mus81-Mms4 endonuclease. Fricke WM, Bastin-Shanower SA, Brill SJ DNA Repair (Amst) Jan. 3, 2005
Roles of SGS1, MUS81, and RAD51 in the repair of lagging-strand replication defects in Saccharomyces cerevisiae. Ii M, Brill SJ Curr Genet Oct. 1, 2005
A multidimensional chromatography technology for in-depth phosphoproteome analysis. Albuquerque CP, Smolka MB, Payne SH, Bafna V, Eng J, Zhou H Mol Cell Proteomics July 1, 2008

Last modification of this entry: Oct. 13, 2010.

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