ID FEN1_YEAST Reviewed; 382 AA.
AC P26793; D6VXH5;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 27-MAR-2024, entry version 198.
DE RecName: Full=Flap endonuclease 1 {ECO:0000255|HAMAP-Rule:MF_03140};
DE Short=FEN-1 {ECO:0000255|HAMAP-Rule:MF_03140};
DE EC=3.1.-.- {ECO:0000255|HAMAP-Rule:MF_03140};
DE AltName: Full=Flap structure-specific endonuclease 1 {ECO:0000255|HAMAP-Rule:MF_03140};
DE AltName: Full=RAD2 homolog nuclease 1;
DE Short=RTH1 nuclease;
DE AltName: Full=Structure-specific endonuclease RAD27;
GN Name=RAD27 {ECO:0000255|HAMAP-Rule:MF_03140};
GN Synonyms=FEN1 {ECO:0000255|HAMAP-Rule:MF_03140}, RTH1;
GN OrderedLocusNames=YKL113C; ORFNames=YKL510;
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 [GENOMIC DNA].
RX PubMed=1561835; DOI=10.1002/yea.320080207;
RA Jacquier A., Legrain P., Dujon B.;
RT "Sequence of a 10.7 kb segment of yeast chromosome XI identifies the APN1
RT and the BAF1 loci and reveals one tRNA gene and several new open reading
RT frames including homologs to RAD2 and kinases.";
RL Yeast 8:121-132(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8196765; DOI=10.1038/369371a0;
RA Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V.,
RA Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P.,
RA Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L.,
RA Daignan-Fornier B., del Rey F., Dion C., Domdey H., Duesterhoeft A.,
RA Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H.,
RA Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L.,
RA Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M.,
RA Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H.,
RA Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J.,
RA Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H.,
RA Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J.,
RA Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S.,
RA Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F.,
RA Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R.,
RA Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W.,
RA Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M.,
RA Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C.,
RA Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H.,
RA Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L.,
RA van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S.,
RA von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M.,
RA Becker I., Mewes H.-W.;
RT "Complete DNA sequence of yeast chromosome XI.";
RL Nature 369:371-378(1994).
RN [3]
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 [4]
RP PROTEIN SEQUENCE OF 284-298, FUNCTION, AND EXONUCLEASE AND RNASE H
RP ACTIVITIES.
RX PubMed=9166764; DOI=10.1021/bi962889v;
RA Zhu F.X., Biswas E.E., Biswas S.B.;
RT "Purification and characterization of the DNA polymerase alpha associated
RT exonuclease: the RTH1 gene product.";
RL Biochemistry 36:5947-5954(1997).
RN [5]
RP CHARACTERIZATION.
RX PubMed=7926735; DOI=10.1101/gad.8.11.1344;
RA Harrington J.J., Lieber M.R.;
RT "Functional domains within FEN-1 and RAD2 define a family of structure-
RT specific endonucleases: implications for nucleotide excision repair.";
RL Genes Dev. 8:1344-1355(1994).
RN [6]
RP CHARACTERIZATION.
RX PubMed=7814325; DOI=10.1128/jb.177.2.364-371.1995;
RA Reagan M.S., Pittenger C., Siede W., Friedberg E.C.;
RT "Characterization of a mutant strain of Saccharomyces cerevisiae with a
RT deletion of the RAD27 gene, a structural homolog of the RAD2 nucleotide
RT excision repair gene.";
RL J. Bacteriol. 177:364-371(1995).
RN [7]
RP INTERACTION WITH POL30, AND MUTAGENESIS OF 346-PHE-PHE-347.
RX PubMed=10899134; DOI=10.1093/emboj/19.14.3811;
RA Gomes X.V., Burgers P.M.;
RT "Two modes of FEN1 binding to PCNA regulated by DNA.";
RL EMBO J. 19:3811-3821(2000).
RN [8]
RP FUNCTION, ENDONUCLEASE ACTIVITY, SUBSTRATE SPECIFICITY, AND MUTAGENESIS OF
RP GLY-240.
RX PubMed=11825897; DOI=10.1074/jbc.m110662200;
RA Kao H.I., Henricksen L.A., Liu Y., Bambara R.A.;
RT "Cleavage specificity of Saccharomyces cerevisiae flap endonuclease 1
RT suggests a double-flap structure as the cellular substrate.";
RL J. Biol. Chem. 277:14379-14389(2002).
RN [9]
RP FUNCTION.
RX PubMed=12424238; DOI=10.1074/jbc.m209801200;
RA Ayyagari R., Gomes X.V., Gordenin D.A., Burgers P.M.;
RT "Okazaki fragment maturation in yeast. I. Distribution of functions between
RT FEN1 and DNA2.";
RL J. Biol. Chem. 278:1618-1625(2003).
RN [10]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [11]
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 [12]
RP FUNCTION, AND MUTAGENESIS OF GLY-67.
RX PubMed=16837458; DOI=10.1074/jbc.m604805200;
RA Rossi M.L., Bambara R.A.;
RT "Reconstituted Okazaki fragment processing indicates two pathways of primer
RT removal.";
RL J. Biol. Chem. 281:26051-26061(2006).
RN [13]
RP FUNCTION, ENDONUCLEASE AND EXONUCLEASE ACTIVITIES, AND MUTAGENESIS OF
RP GLU-176.
RX PubMed=17138563; DOI=10.1074/jbc.m606582200;
RA Singh P., Zheng L., Chavez V., Qiu J., Shen B.;
RT "Concerted action of exonuclease and Gap-dependent endonuclease activities
RT of FEN-1 contributes to the resolution of triplet repeat sequences
RT (CTG)n- and (GAA)n-derived secondary structures formed during maturation of
RT Okazaki fragments.";
RL J. Biol. Chem. 282:3465-3477(2007).
RN [14]
RP FUNCTION IN RDNA REPLICATION AND REPAIR.
RX PubMed=18443037; DOI=10.1128/mcb.00200-08;
RA Guo Z., Qian L., Liu R., Dai H., Zhou M., Zheng L., Shen B.;
RT "Nucleolar localization and dynamic roles of flap endonuclease 1 in
RT ribosomal DNA replication and damage repair.";
RL Mol. Cell. Biol. 28:4310-4319(2008).
RN [15]
RP FUNCTION IN MITOCHONDRIAL DNA REPAIR, AND SUBCELLULAR LOCATION.
RX PubMed=19699691; DOI=10.1016/j.dnarep.2009.07.008;
RA Kalifa L., Beutner G., Phadnis N., Sheu S.S., Sia E.A.;
RT "Evidence for a role of FEN1 in maintaining mitochondrial DNA integrity.";
RL DNA Repair 8:1242-1249(2009).
RN [16]
RP FUNCTION IN DNA REPAIR.
RX PubMed=19075004; DOI=10.1128/mcb.01499-08;
RA Ma W., Panduri V., Sterling J.F., Van Houten B., Gordenin D.A.,
RA Resnick M.A.;
RT "The transition of closely opposed lesions to double-strand breaks during
RT long-patch base excision repair is prevented by the coordinated action of
RT DNA polymerase delta and Rad27/Fen1.";
RL Mol. Cell. Biol. 29:1212-1221(2009).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: Structure-specific nuclease with 5'-flap endonuclease and 5'-
CC 3' exonuclease activities involved in DNA replication and repair.
CC During DNA replication, cleaves the 5'-overhanging flap structure that
CC is generated by displacement synthesis when DNA polymerase encounters
CC the 5'-end of a downstream Okazaki fragment. It enters the flap from
CC the 5'-end and then tracks to cleave the flap base, leaving a nick for
CC ligation. Also involved in the long patch base excision repair (LP-BER)
CC pathway, by cleaving within the apurinic/apyrimidinic (AP) site-
CC terminated flap. Acts as a genome stabilization factor that prevents
CC flaps from equilibrating into structures that lead to duplications and
CC deletions. Also possesses 5'-3' exonuclease activity on nicked or
CC gapped double-stranded DNA, and exhibits RNase H activity. Also
CC involved in replication and repair of rDNA and in repairing
CC mitochondrial DNA. {ECO:0000255|HAMAP-Rule:MF_03140,
CC ECO:0000269|PubMed:11825897, ECO:0000269|PubMed:12424238,
CC ECO:0000269|PubMed:16837458, ECO:0000269|PubMed:17138563,
CC ECO:0000269|PubMed:18443037, ECO:0000269|PubMed:19075004,
CC ECO:0000269|PubMed:19699691, ECO:0000269|PubMed:9166764}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03140};
CC Note=Binds 2 magnesium ions per subunit. They probably participate in
CC the reaction catalyzed by the enzyme. May bind an additional third
CC magnesium ion after substrate binding. {ECO:0000255|HAMAP-
CC Rule:MF_03140};
CC -!- SUBUNIT: Interacts with PCNA (POL30). Three molecules of RAD27 bind to
CC one PCNA trimer with each molecule binding to one PCNA monomer. PCNA
CC stimulates the nuclease activity without altering cleavage specificity.
CC {ECO:0000269|PubMed:10899134}.
CC -!- INTERACTION:
CC P26793; P38859: DNA2; NbExp=3; IntAct=EBI-14693, EBI-5973;
CC P26793; P15873: POL30; NbExp=7; IntAct=EBI-14693, EBI-12993;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus. Nucleus, nucleoplasm.
CC Mitochondrion. Note=Resides mostly in the nucleoli and relocalizes to
CC the nucleoplasm upon DNA damage.
CC -!- PTM: Phosphorylated. Phosphorylation upon DNA damage induces
CC relocalization to the nuclear plasma. {ECO:0000255|HAMAP-
CC Rule:MF_03140}.
CC -!- MISCELLANEOUS: Present with 6120 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the XPG/RAD2 endonuclease family. FEN1
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_03140}.
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DR EMBL; S93804; AAB21998.1; -; Genomic_DNA.
DR EMBL; Z28113; CAA81953.1; -; Genomic_DNA.
DR EMBL; BK006944; DAA09045.1; -; Genomic_DNA.
DR PIR; S22267; S22267.
DR RefSeq; NP_012809.1; NM_001179679.1.
DR AlphaFoldDB; P26793; -.
DR SMR; P26793; -.
DR BioGRID; 34021; 630.
DR DIP; DIP-2325N; -.
DR ELM; P26793; -.
DR IntAct; P26793; 3.
DR MINT; P26793; -.
DR STRING; 4932.YKL113C; -.
DR iPTMnet; P26793; -.
DR MaxQB; P26793; -.
DR PaxDb; 4932-YKL113C; -.
DR PeptideAtlas; P26793; -.
DR EnsemblFungi; YKL113C_mRNA; YKL113C; YKL113C.
DR GeneID; 853747; -.
DR KEGG; sce:YKL113C; -.
DR AGR; SGD:S000001596; -.
DR SGD; S000001596; RAD27.
DR VEuPathDB; FungiDB:YKL113C; -.
DR eggNOG; KOG2519; Eukaryota.
DR GeneTree; ENSGT00940000155807; -.
DR HOGENOM; CLU_032444_2_0_1; -.
DR InParanoid; P26793; -.
DR OMA; GSQDYDS; -.
DR OrthoDB; 5479162at2759; -.
DR BioCyc; YEAST:G3O-31898-MONOMER; -.
DR Reactome; R-SCE-69166; Removal of the Flap Intermediate.
DR BioGRID-ORCS; 853747; 2 hits in 10 CRISPR screens.
DR PRO; PR:P26793; -.
DR Proteomes; UP000002311; Chromosome XI.
DR RNAct; P26793; Protein.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:SGD.
DR GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:0008409; F:5'-3' exonuclease activity; IDA:SGD.
DR GO; GO:0017108; F:5'-flap endonuclease activity; IDA:SGD.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0006284; P:base-excision repair; IEA:UniProtKB-UniRule.
DR GO; GO:0043137; P:DNA replication, removal of RNA primer; IDA:SGD.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IDA:SGD.
DR GO; GO:0007534; P:gene conversion at mating-type locus; IMP:SGD.
DR GO; GO:0035753; P:maintenance of DNA trinucleotide repeats; IMP:SGD.
DR CDD; cd09907; H3TH_FEN1-Euk; 1.
DR CDD; cd09867; PIN_FEN1; 1.
DR Gene3D; 1.10.150.20; 5' to 3' exonuclease, C-terminal subdomain; 1.
DR Gene3D; 3.40.50.1010; 5'-nuclease; 1.
DR HAMAP; MF_00614; Fen; 1.
DR InterPro; IPR036279; 5-3_exonuclease_C_sf.
DR InterPro; IPR023426; Flap_endonuc.
DR InterPro; IPR008918; HhH2.
DR InterPro; IPR029060; PIN-like_dom_sf.
DR InterPro; IPR006086; XPG-I_dom.
DR InterPro; IPR006084; XPG/Rad2.
DR InterPro; IPR019974; XPG_CS.
DR InterPro; IPR006085; XPG_DNA_repair_N.
DR PANTHER; PTHR11081:SF9; FLAP ENDONUCLEASE 1; 1.
DR PANTHER; PTHR11081; FLAP ENDONUCLEASE FAMILY MEMBER; 1.
DR Pfam; PF00867; XPG_I; 1.
DR Pfam; PF00752; XPG_N; 1.
DR PRINTS; PR00853; XPGRADSUPER.
DR SMART; SM00279; HhH2; 1.
DR SMART; SM00484; XPGI; 1.
DR SMART; SM00485; XPGN; 1.
DR SUPFAM; SSF47807; 5' to 3' exonuclease, C-terminal subdomain; 1.
DR SUPFAM; SSF88723; PIN domain-like; 1.
DR PROSITE; PS00841; XPG_1; 1.
DR PROSITE; PS00842; XPG_2; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; DNA damage; DNA repair; DNA replication;
KW Endonuclease; Exonuclease; Hydrolase; Magnesium; Metal-binding;
KW Mitochondrion; Nuclease; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..382
FT /note="Flap endonuclease 1"
FT /id="PRO_0000154038"
FT REGION 1..105
FT /note="N-domain"
FT REGION 120..251
FT /note="I-domain"
FT REGION 339..347
FT /note="Interaction with PCNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT REGION 358..382
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 359..373
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 34
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 47
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 71
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 87
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 156
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 156
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 158
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 177
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 179
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 229
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 231
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 231
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT MUTAGEN 67
FT /note="G->S: Deficient in double and single flap
FT endonuclease cleavage and exonucleolytic cleavage."
FT /evidence="ECO:0000269|PubMed:16837458"
FT MUTAGEN 176
FT /note="E->A: Deficient in exonuclease and gap endonuclease
FT activities, but retains almost all of its flap endonuclease
FT activity."
FT /evidence="ECO:0000269|PubMed:17138563"
FT MUTAGEN 240
FT /note="G->D: Can only cleave double-flap structures with a
FT 3' 1-nucleotide tail. Has no exonuclease activity."
FT /evidence="ECO:0000269|PubMed:11825897"
FT MUTAGEN 346..347
FT /note="FF->GA: Reduces interaction with POL30 more than 100
FT fold."
FT /evidence="ECO:0000269|PubMed:10899134"
SQ SEQUENCE 382 AA; 43279 MW; 1F54B08720121C8C CRC64;
MGIKGLNAII SEHVPSAIRK SDIKSFFGRK VAIDASMSLY QFLIAVRQQD GGQLTNEAGE
TTSHLMGMFY RTLRMIDNGI KPCYVFDGKP PDLKSHELTK RSSRRVETEK KLAEATTELE
KMKQERRLVK VSKEHNEEAQ KLLGLMGIPY IIAPTEAEAQ CAELAKKGKV YAAASEDMDT
LCYRTPFLLR HLTFSEAKKE PIHEIDTELV LRGLDLTIEQ FVDLCIMLGC DYCESIRGVG
PVTALKLIKT HGSIEKIVEF IESGESNNTK WKIPEDWPYK QARMLFLDPE VIDGNEINLK
WSPPKEKELI EYLCDDKKFS EERVKSGISR LKKGLKSGIQ GRLDGFFQVV PKTKEQLAAA
AKRAQENKKL NKNKNKVTKG RR
//
