MUS81_YEAST
ID MUS81_YEAST Reviewed; 632 AA.
AC Q04149; D6VT20;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Crossover junction endonuclease MUS81;
DE EC=3.1.22.-;
DE AltName: Full=MMS and UV-sensitive protein 81;
GN Name=MUS81; Synonyms=SLX3; OrderedLocusNames=YDR386W; ORFNames=D9509.6;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169867;
RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA Mewes H.-W., Zollner A., Zaccaria P.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL Nature 387:75-78(1997).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [3]
RP FUNCTION, DNA REPAIR, AND INTERACTION WITH RAD54.
RX PubMed=10905349; DOI=10.1007/s004380000241;
RA Interthal H., Heyer W.-D.;
RT "MUS81 encodes a novel helix-hairpin-helix protein involved in the response
RT to UV- and methylation-induced DNA damage in Saccharomyces cerevisiae.";
RL Mol. Gen. Genet. 263:812-827(2000).
RN [4]
RP FUNCTION, PROCESSING OF STALLED REPLICATION FORK, AND INTERACTION WITH
RP MMS4.
RX PubMed=11641278; DOI=10.1101/gad.932201;
RA Kaliraman V., Mullen J.R., Fricke W.M., Bastin-Shanower S.A., Brill S.J.;
RT "Functional overlap between Sgs1-Top3 and the Mms4-Mus81 endonuclease.";
RL Genes Dev. 15:2730-2740(2001).
RN [5]
RP FUNCTION, AND INTERACTION WITH MMS4.
RX PubMed=11139495; DOI=10.1093/genetics/157.1.103;
RA Mullen J.R., Kaliraman V., Ibrahim S.S., Brill S.J.;
RT "Requirement for three novel protein complexes in the absence of the Sgs1
RT DNA helicase in Saccharomyces cerevisiae.";
RL Genetics 157:103-118(2001).
RN [6]
RP FUNCTION.
RX PubMed=12475932; DOI=10.1073/pnas.252652399;
RA Fabre F., Chan A., Heyer W.-D., Gangloff S.;
RT "Alternate pathways involving Sgs1/Top3, Mus81/ Mms4, and Srs2 prevent
RT formation of toxic recombination intermediates from single-stranded gaps
RT created by DNA replication.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16887-16892(2002).
RN [7]
RP ERRATUM OF PUBMED:12475932.
RA Fabre F., Chan A., Heyer W.-D., Gangloff S.;
RL Proc. Natl. Acad. Sci. U.S.A. 100:1462-1462(2002).
RN [8]
RP FUNCTION, INTERACTION WITH MMS4, AND SUBCELLULAR LOCATION.
RX PubMed=14642571; DOI=10.1016/j.dnarep.2003.08.013;
RA Fu Y., Xiao W.;
RT "Functional domains required for the Saccharomyces cerevisiae Mus81-Mms4
RT endonuclease complex formation and nuclear localization.";
RL DNA Repair 2:1435-1447(2003).
RN [9]
RP FUNCTION, CROSSOVER WITHOUT DOUBLE HOLLIDAY JUNCTION, AND MUTAGENESIS OF
RP 414-ASP-ASP-415.
RX PubMed=12750322; DOI=10.1093/genetics/164.1.81;
RA de los Santos T., Hunter N., Lee C., Larkin B., Loidl J.,
RA Hollingsworth N.M.;
RT "The Mus81/Mms4 endonuclease acts independently of double-Holliday junction
RT resolution to promote a distinct subset of crossovers during meiosis in
RT budding yeast.";
RL Genetics 164:81-94(2003).
RN [10]
RP FUNCTION.
RX PubMed=12473680; DOI=10.1074/jbc.m210006200;
RA Whitby M.C., Osman F., Dixon J.;
RT "Cleavage of model replication forks by fission yeast Mus81-Eme1 and
RT budding yeast Mus81-Mms4.";
RL J. Biol. Chem. 278:6928-6935(2003).
RN [11]
RP FUNCTION, AND CLEAVAGE SITE SELECTION.
RX PubMed=12724407; DOI=10.1128/mcb.23.10.3487-3496.2003;
RA Bastin-Shanower S.A., Fricke W.M., Mullen J.R., Brill S.J.;
RT "The mechanism of Mus81-Mms4 cleavage site selection distinguishes it from
RT the homologous endonuclease Rad1-Rad10.";
RL Mol. Cell. Biol. 23:3487-3496(2003).
RN [12]
RP FUNCTION, AND CROSSOVER WITHOUT DOUBLE HOLLIDAY JUNCTION.
RX PubMed=14527420; DOI=10.1016/s1097-2765(03)00343-5;
RA Osman F., Dixon J., Doe C.L., Whitby M.C.;
RT "Generating crossovers by resolution of nicked Holliday junctions: a role
RT for Mus81-Eme1 in meiosis.";
RL Mol. Cell 12:761-774(2003).
RN [13]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [14]
RP FUNCTION.
RX PubMed=16193328; DOI=10.1007/s00294-005-0014-5;
RA Ii M., Brill S.J.;
RT "Roles of SGS1, MUS81, and RAD51 in the repair of lagging-strand
RT replication defects in Saccharomyces cerevisiae.";
RL Curr. Genet. 48:213-225(2005).
RN [15]
RP FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND INTERACTION WITH
RP MMS4.
RX PubMed=15590332; DOI=10.1016/j.dnarep.2004.10.001;
RA Fricke W.M., Bastin-Shanower S.A., Brill S.J.;
RT "Substrate specificity of the Saccharomyces cerevisiae Mus81-Mms4
RT endonuclease.";
RL DNA Repair 4:243-251(2005).
RN [16]
RP REVIEW.
RX PubMed=14752007; DOI=10.1101/gad.1165904;
RA Hollingsworth N.M., Brill S.J.;
RT "The Mus81 solution to resolution: generating meiotic crossovers without
RT Holliday junctions.";
RL Genes Dev. 18:117-125(2004).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
CC -!- FUNCTION: Interacts with MMS4 to form a DNA structure-specific
CC endonuclease with substrate preference for branched DNA structures with
CC a 5'-end at the branch nick. Typical substrates include 3'-flap
CC structures, D-loops, replication forks with regressed leading strands
CC and nicked Holliday junctions. Cleavage probably occurs approximately
CC half a helical turn upstream of the free 5'-end in these structures.
CC May be required in mitosis for the processing of stalled replication
CC fork intermediates arising spontaneously or subsequent to treatment
CC with DNA damaging agents such as methylmethane sulfonate (MMS),
CC camptothecin (CPT) or UV. May be required in meiosis for the repair of
CC meiosis-specific double strand breaks subsequent to single-end invasion
CC (SEI). This involves consecutive cleavage of D-loops and nicked
CC Holliday junctions leading to sister chromatid crossover. In contrast
CC to MSH4-MSH5 dependent crossover, double Holliday junctions do not seem
CC to be involved. Spore formation and viability are severely impaired in
CC deletion strains. {ECO:0000269|PubMed:10905349,
CC ECO:0000269|PubMed:11139495, ECO:0000269|PubMed:11641278,
CC ECO:0000269|PubMed:12473680, ECO:0000269|PubMed:12475932,
CC ECO:0000269|PubMed:12724407, ECO:0000269|PubMed:12750322,
CC ECO:0000269|PubMed:14527420, ECO:0000269|PubMed:14642571,
CC ECO:0000269|PubMed:15590332, ECO:0000269|PubMed:16193328}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15590332};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:15590332};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=31.1 nM for a nicked Holliday junction
CC {ECO:0000269|PubMed:15590332};
CC KM=6.84 nM for a regressed leading strand replication fork
CC {ECO:0000269|PubMed:15590332};
CC KM=4.8 nM for a 3'-flap structure {ECO:0000269|PubMed:15590332};
CC KM=3.45 nM for a nicked duplex {ECO:0000269|PubMed:15590332};
CC KM=14.0 nM for a regressed lagging strand replication fork
CC {ECO:0000269|PubMed:15590332};
CC KM=245 nM for a Y structure {ECO:0000269|PubMed:15590332};
CC KM=173 nM for a double flap structure {ECO:0000269|PubMed:15590332};
CC Vmax=55.6 nmol/min/ng enzyme with a nicked Holliday junction as
CC substrate {ECO:0000269|PubMed:15590332};
CC Vmax=31.3 nmol/min/ng enzyme with a regressed leading strand
CC replication fork as substrate {ECO:0000269|PubMed:15590332};
CC Vmax=24.4 nmol/min/ng enzyme with a 3'-flap structure as substrate
CC {ECO:0000269|PubMed:15590332};
CC Vmax=2.21 nmol/min/ng enzyme with a nicked duplex as substrate
CC {ECO:0000269|PubMed:15590332};
CC Vmax=0.832 nmol/min/ng enzyme with a regressed lagging strand
CC replication fork as subsystrate {ECO:0000269|PubMed:15590332};
CC Vmax=0.0468 nmol/min/ng enzyme with a Y structure as substrate
CC {ECO:0000269|PubMed:15590332};
CC Vmax=0.0879 nmol/min/ng enzyme with a double flap structure as
CC substrate {ECO:0000269|PubMed:15590332};
CC pH dependence:
CC Optimum pH is 8.0 for the cleavage of a 3'-flap structure.
CC {ECO:0000269|PubMed:15590332};
CC -!- SUBUNIT: Interacts with MMS4 and RAD54. {ECO:0000269|PubMed:10905349,
CC ECO:0000269|PubMed:11139495, ECO:0000269|PubMed:11641278,
CC ECO:0000269|PubMed:14642571, ECO:0000269|PubMed:15590332}.
CC -!- INTERACTION:
CC Q04149; P38257: MMS4; NbExp=4; IntAct=EBI-33508, EBI-21547;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14642571}.
CC -!- MISCELLANEOUS: Two distinct classes of meiotic crossovers have been
CC demonstrated in budding yeast. Class I crossovers exhibit crossover
CC interference and require MSH4 and MSH5 for their resolution, while
CC class II crossovers exhibit no crossover interference and require MUS81
CC and MMS4. While class I crossovers represent the majority of crossovers
CC in S.cerevisiae, they are virtually absent in S.pombe, which lacks
CC orthologs of MSH4 and MSH5.
CC -!- MISCELLANEOUS: Present with 300 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the XPF family. {ECO:0000305}.
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DR EMBL; U32274; AAB64828.1; -; Genomic_DNA.
DR EMBL; BK006938; DAA12230.1; -; Genomic_DNA.
DR PIR; S69670; S69670.
DR RefSeq; NP_010674.3; NM_001180694.3.
DR AlphaFoldDB; Q04149; -.
DR SMR; Q04149; -.
DR BioGRID; 32447; 251.
DR ComplexPortal; CPX-1670; Deoxyribonuclease complex MUS81-MMS4.
DR DIP; DIP-1009N; -.
DR IntAct; Q04149; 55.
DR MINT; Q04149; -.
DR STRING; 4932.YDR386W; -.
DR iPTMnet; Q04149; -.
DR MaxQB; Q04149; -.
DR PaxDb; Q04149; -.
DR PRIDE; Q04149; -.
DR EnsemblFungi; YDR386W_mRNA; YDR386W; YDR386W.
DR GeneID; 851994; -.
DR KEGG; sce:YDR386W; -.
DR SGD; S000002794; MUS81.
DR VEuPathDB; FungiDB:YDR386W; -.
DR eggNOG; KOG2379; Eukaryota.
DR GeneTree; ENSGT00390000005498; -.
DR HOGENOM; CLU_014329_1_0_1; -.
DR InParanoid; Q04149; -.
DR OMA; WIKEWLD; -.
DR BioCyc; YEAST:G3O-29934-MON; -.
DR Reactome; R-SCE-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR PRO; PR:Q04149; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; Q04149; protein.
DR GO; GO:1905347; C:endodeoxyribonuclease complex; IPI:ComplexPortal.
DR GO; GO:0048476; C:Holliday junction resolvase complex; IDA:SGD.
DR GO; GO:0043596; C:nuclear replication fork; IDA:ComplexPortal.
DR GO; GO:0005634; C:nucleus; IMP:SGD.
DR GO; GO:0048257; F:3'-flap endonuclease activity; IBA:GO_Central.
DR GO; GO:0008821; F:crossover junction endodeoxyribonuclease activity; IEA:InterPro.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0004857; F:enzyme inhibitor activity; IDA:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:SGD.
DR GO; GO:0000737; P:DNA catabolic process, endonucleolytic; IEA:InterPro.
DR GO; GO:0006265; P:DNA topological change; IGI:SGD.
DR GO; GO:0000727; P:double-strand break repair via break-induced replication; IMP:SGD.
DR GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; IBA:GO_Central.
DR GO; GO:0051097; P:negative regulation of helicase activity; IDA:SGD.
DR GO; GO:0007131; P:reciprocal meiotic recombination; IGI:SGD.
DR GO; GO:0000712; P:resolution of meiotic recombination intermediates; IGI:SGD.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 1.10.150.110; -; 1.
DR Gene3D; 1.10.150.670; -; 1.
DR InterPro; IPR027421; DNA_pol_lamdba_lyase_dom_sf.
DR InterPro; IPR042530; EME1/EME2_C.
DR InterPro; IPR006166; ERCC4_domain.
DR InterPro; IPR033309; Mus81.
DR InterPro; IPR011335; Restrct_endonuc-II-like.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR PANTHER; PTHR13451; PTHR13451; 1.
DR Pfam; PF02732; ERCC4; 1.
DR SMART; SM00891; ERCC4; 1.
DR SUPFAM; SSF47802; SSF47802; 1.
DR SUPFAM; SSF52980; SSF52980; 1.
PE 1: Evidence at protein level;
KW DNA damage; DNA recombination; DNA repair; Endonuclease; Hydrolase;
KW Magnesium; Manganese; Meiosis; Metal-binding; Nuclease; Nucleus;
KW Reference proteome.
FT CHAIN 1..632
FT /note="Crossover junction endonuclease MUS81"
FT /id="PRO_0000198861"
FT DOMAIN 351..448
FT /note="ERCC4"
FT REGION 109..129
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 527..632
FT /note="Interaction with MMS4"
FT ACT_SITE 415
FT /evidence="ECO:0000305"
FT MUTAGEN 414..415
FT /note="DD->AA: In allele MUS81-DD; abrogates endonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:12750322"
SQ SEQUENCE 632 AA; 72309 MW; F73FA3856C5F87F1 CRC64;
MELSSNLKDL YIEWLQELVD GLTPKQEQLK IAYEKAKRNL QNAEGSFYYP TDLKKVKGIG
NTIIKRLDTK LRNYCKIHHI SPVEAPSLTQ TSSTRPPKRT TTALRSIVNS CENDKNEAPE
EKGTKKRKTR KYIPKKRSGG YAILLSLLEL NAIPRGVSKE QIIEVAGKYS DHCMTPNFST
KEFYGAWSSI AALKKHSLVL EEGRPKRYSL TEEGVELTKS LKTADGISFP KENEEPNEYS
VTRNESSEFT ANLTDLRGEY GKEEEPCDIN NTSFMLDITF QDLSTPQRLQ NNVFKNDRLN
SQTNISSHKL EEVSDDQTVP DSALKAKSTI KRRRYNGVSY ELWCSGDFEV FPIIDHREIK
SQSDREFFSR AFERKGMKSE IRQLALGDII WVAKNKNTGL QCVLNTIVER KRLDDLALSI
RDNRFMEQKN RLEKSGCEHK YYLIEETMSG NIGNMNEALK TALWVILVYY KFSMIRTCNS
DETVEKIHAL HTVISHHYSQ KDLIVIFPSD LKSKDDYKKV LLQFRREFER KGGIECCHNL
ECFQELMGKG DLKTVGELTI HVLMLVKGIS LEKAVAIQEI FPTLNKILMA YKTCSSEEEA
KLLMFNVLGD APGAKKITKS LSEKIYDAFG KL
