DNA endonuclease SAE2 - Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)

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P46946 (COM1_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 75. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
DNA endonuclease SAE2
EC=3.1.-.-

Alternative name(s):
Completion of meiotic recombination protein 1
Sporulation in the absence of SPO11 protein 2

Gene names

Name:	SAE2
Synonyms:	COM1
Ordered Locus Names:	YGL175C
ORF Names:	G1639

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

Protein attributes

Sequence length	345 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Endonuclease that cooperates with the MRX complex in processing meiotic and mitotic double-strand breaks by allowing the endonucleolytic removal of SPO11 from the break sites and ensuring both resection and intrachromosomal association of the broken ends. Required for proper recovery from checkpoint-mediated cell cycle arrest after DNA damage. MRX complex and SAE2 remove a small oligonucleotide(s) from the DNA ends to form an early intermediate which is rapidly processed by EXO1 and/or SGS1 to generate extensive tracts of single-stranded DNA that serve as substrate for RAD51. Plays a transitional role in the dissociation of MRE11 from, and the recruitment of RAD52 to, repair foci. Ensures that both ends of a DSB participate in a recombination event and impairs the formation of palindromic structures in the genome. With TEL1, promotes microhomology-mediated end joining (MMEJ) but inhibits non-homologous end joining (NHEJ), likely by regulating MRE11-dependent ssDNA accumulation at DNA break. SAE2 and MRX are particularly important for removal of hairpins, bulky adducts and other irregular end structures. Facilitates telomere length reequilibration and subsequent checkpoint switch off. Involved in homing efficiency of VMA1 intein VDE and in repair of transposon excision sites. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.25 Ref.26 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33
Subunit structure	Dimer or multimer. Interacts with MRE11. Ref.24
Subcellular location	Cytoplasm. Nucleus. Note: Accumulates in foci at the precise time when MRE11 foci disassemble and RAD52 foci assemble. Remains associated with DSBs along with MRE11 in nuclease-deficient cells. Ref.12 Ref.14 Ref.26
Post-translational modification	Phosphorylated forms accumulate periodically during the unperturbed cell cycle and in response to DNA damage in G2. Phosphorylated by MEC1 and TEL1. Mutagenesis experiments showed that several of the 5 residues located in canonical (S/T)Q motifs, which are favored for phosphorylation by ATM/ATR kinases (Ser-73, Thr-90, Ser-249, Thr-279 and Ser-289) may be phosphorylated. Phosphorylated at Ser-267 by CDC28 which is required to initiate meiotic DSB resection by allowing SPO11 removal from DSB ends. Ref.16 Ref.21 Ref.26 Ref.27 Ref.28 Ref.32 Ref.33
Miscellaneous	Present with 1030 molecules/cell in log phase SD medium. Ref.13
Sequence similarities	Belongs to the COM1/SAE2/CtIP family.

Ontologies

Keywords
Biological process	DNA damage DNA repair Meiosis
Cellular component	Cytoplasm Nucleus
Ligand	DNA-binding
Molecular function	Endonuclease Hydrolase Nuclease
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	DNA catabolic process, endonucleolytic Inferred from direct assay. Source: SGD gene conversion at mating-type locus, DNA double-strand break processing Inferred from mutant phenotype Ref.29. Source: SGD meiosis Inferred from electronic annotation. Source: UniProtKB-KW meiotic DNA double-strand break processing Inferred from mutant phenotype Ref.1. Source: SGD
Cellular component	cytoplasm Inferred from direct assay Ref.12. Source: SGD nucleoplasm Traceable author statement. Source: Reactome
Molecular function	double-stranded DNA binding Inferred from direct assay. Source: SGD single-stranded DNA specific endodeoxyribonuclease activity Inferred from direct assay. Source: SGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 345

345

DNA endonuclease SAE2

PRO_0000097565

Regions

Region

21 – 172

152

DNA-binding

Amino acid modifications

Modified residue

177

Phosphoserine Ref.27

Modified residue

267

Phosphoserine; by CDC28 Ref.28 Ref.32

Experimental info

Mutagenesis

S → A: Reduces DNA damage-induced phosphorylation; when associated with A-73, A-75, A-76 and A-90. Ref.16

Mutagenesis

S → A: Reduces DNA damage-induced phosphorylation; when associated with A-73, A-75, A-76 and A-90. Abolishes DNA damage-induced phosphorylation and function in DNA repair; when associated with A-90, A-249, A-279 and A-289. Ref.16 Ref.21 Ref.26

Mutagenesis

T → A: Reduces DNA damage-induced phosphorylation; when associated with A-72, A-75, A-76 and A-90. Ref.16

Mutagenesis

S → A: Reduces DNA damage-induced phosphorylation; when associated with A-72, A-73, A-75 and A-90. Ref.16

Mutagenesis

T → A: Reduces DNA damage-induced phosphorylation; when associated with A-72, A-73, A-75 and A-76. Abolishes DNA damage-induced phosphorylation and function in DNA repair; when associated with A-73, A-249, A-279 and A-289. Ref.16 Ref.21 Ref.26

Mutagenesis

223

R → A: Leads to camptothecin hypersensitivity and loss of function; when associated with A-225. Ref.28

Mutagenesis

225

L → A: Leads to camptothecin hypersensitivity and loss of function; when associated with A-223. Ref.28

Mutagenesis

249

S → A: Reduces DNA damage-induced phosphorylation; when associated with A-278, A-279, and A-289. Abolishes DNA damage-induced phosphorylation and function in DNA repair; when associated with A-73, A-90, A-279 and A-289. Ref.16 Ref.21 Ref.26

Mutagenesis

267

S → A: Leads to camptothecin hypersensitivity and loss of function. Ref.28 Ref.32

Mutagenesis

267

S → E: Leads to constitutive activation of the DNA repair function. Ref.28 Ref.32

Mutagenesis

270

G → D: Abolishes DNA-binding and endonuclease activity. Ref.25

Mutagenesis

278

S → A: Reduces DNA damage-induced phosphorylation; when associated with A-249, A-279, and A-289. Ref.16

Mutagenesis

279

T → A: Reduces DNA damage-induced phosphorylation; when associated with A-249, A-278, and A-289. Abolishes DNA damage-induced phosphorylation and function in DNA repair; when associated with A-73, A-90, A-249 and A-289. Ref.16 Ref.21 Ref.26

Mutagenesis

289

S → A: Reduces DNA damage-induced phosphorylation; when associated with A-249, A-278, and A-279. Abolishes DNA damage-induced phosphorylation and function in DNA repair; when associated with A-73, A-90, A-249 and A-279. Ref.16 Ref.21 Ref.26

Sequences

Sequence

Length

Mass (Da)

Tools

P46946 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 284D57A3C11DD92B
Show »

FASTA

345

40,097

        10         20         30         40         50         60 
MVTGEENVYL KSSLSILKEL SLDELLNVQY DVTTLIAKRV QALQNRNKCV LEEPNSKLAE 

        70         80         90        100        110        120 
ILCHEKNAPQ QSSQTSAGPG EQDSEDFILT QFDEDIKKES AEVHYRNENK HTVQLPLVTM 

       130        140        150        160        170        180 
PPNRHKRKIS EFSSPLNGLN NLSDLEDCSD TVIHEKDNDK ENKTRKLLGI ELENPESTSP 

       190        200        210        220        230        240 
NLYKNVKDNF LFDFNTNPLT KRAWILEDFR PNEDIAPVKR GRRKLERFYA QVGKPEDSKH 

       250        260        270        280        290        300 
RSLSVVIESQ NSDYEFAFDN LRNRSKSPPG FGRLDFPSTQ EGNEDKKKSQ EIIRRKTKYR 

       310        320        330        340 
FLMASNNKIP PYEREYVFKR EQLNQIVDDG CFFWSDKLLQ IYARC

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A general method for identifying recessive diploid-specific mutations in Saccharomyces cerevisiae, its application to the isolation of mutants blocked at intermediate stages of meiotic prophase and characterization of a new gene SAE2." McKee A.H.Z., Kleckner N. Genetics 146:797-816(1997) [PubMed: 9215888] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[2]	"The sequence of an 11.1 kb fragment on the left arm of Saccharomyces cerevisiae chromosome VII reveals six open reading frames including NSP49, KEM1 and four putative new genes." Bertani I., Coglievina M., Zaccaria P., Klima R., Bruschi C.V. Yeast 11:1187-1194(1995) [PubMed: 8619317] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[3]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome VII." Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J., Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M., Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L., Coblenz A., Coglievina M., Coissac E. Kleine K. Nature 387:81-84(1997) [PubMed: 9169869] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[4]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[5]	"Isolation of COM1, a new gene required to complete meiotic double-strand break-induced recombination in Saccharomyces cerevisiae." Prinz S., Amon A., Klein F. Genetics 146:781-795(1997) [PubMed: 9215887] [Abstract] Cited for: FUNCTION.
[6]	"Direct coupling between meiotic DNA replication and recombination initiation." Borde V., Goldman A.S., Lichten M. Science 290:806-809(2000) [PubMed: 11052944] [Abstract] Cited for: FUNCTION.
[7]	"Fidelity of mitotic double-strand-break repair in Saccharomyces cerevisiae: a role for SAE2/COM1." Rattray A.J., McGill C.B., Shafer B.K., Strathern J.N. Genetics 158:109-122(2001) [PubMed: 11333222] [Abstract] Cited for: FUNCTION.
[8]	"Wild-type levels of Spo11-induced DSBs are required for normal single-strand resection during meiosis." Neale M.J., Ramachandran M., Trelles-Sticken E., Scherthan H., Goldman A.S. Mol. Cell 9:835-846(2002) [PubMed: 11983174] [Abstract] Cited for: FUNCTION.
[9]	"The Mre11 complex is required for repair of hairpin-capped double-strand breaks and prevention of chromosome rearrangements." Lobachev K.S., Gordenin D.A., Resnick M.A. Cell 108:183-193(2002) [PubMed: 11832209] [Abstract] Cited for: FUNCTION.
[10]	"VDE-initiated intein homing in Saccharomyces cerevisiae proceeds in a meiotic recombination-like manner." Fukuda T., Nogami S., Ohya Y. Genes Cells 8:587-602(2003) [PubMed: 12839620] [Abstract] Cited for: FUNCTION.
[11]	"Sudden telomere lengthening triggers a Rad53-dependent checkpoint in Saccharomyces cerevisiae." Viscardi V., Baroni E., Romano M., Lucchini G., Longhese M.P. Mol. Biol. Cell 14:3126-3143(2003) [PubMed: 12925751] [Abstract] Cited for: FUNCTION.
[12]	"Global analysis of protein localization in budding yeast." Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K. Nature 425:686-691(2003) [PubMed: 14562095] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[13]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed: 14562106] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[14]	"Choreography of the DNA damage response: spatiotemporal relationships among checkpoint and repair proteins." Lisby M., Barlow J.H., Burgess R.C., Rothstein R. Cell 118:699-713(2004) [PubMed: 15369670] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[15]	"Microhomology-dependent end joining and repair of transposon-induced DNA hairpins by host factors in Saccharomyces cerevisiae." Yu J., Marshall K., Yamaguchi M., Haber J.E., Weil C.F. Mol. Cell. Biol. 24:1351-1364(2004) [PubMed: 14729978] [Abstract] Cited for: FUNCTION.
[16]	"The functions of budding yeast Sae2 in the DNA damage response require Mec1- and Tel1-dependent phosphorylation." Baroni E., Viscardi V., Cartagena-Lirola H., Lucchini G., Longhese M.P. Mol. Cell. Biol. 24:4151-4165(2004) [PubMed: 15121837] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION, MUTAGENESIS OF SER-72; SER-73; THR-75; SER-76; THR-90; SER-249; SER-278; THR-279 AND SER-289.
[17]	"The control of Spo11's interaction with meiotic recombination hotspots." Prieler S., Penkner A., Borde V., Klein F. Genes Dev. 19:255-269(2005) [PubMed: 15655113] [Abstract] Cited for: FUNCTION.
[18]	"A mechanism of palindromic gene amplification in Saccharomyces cerevisiae." Rattray A.J., Shafer B.K., Neelam B., Strathern J.N. Genes Dev. 19:1390-1399(2005) [PubMed: 15937224] [Abstract] Cited for: FUNCTION.
[19]	"Multiple endonucleases function to repair covalent topoisomerase I complexes in Saccharomyces cerevisiae." Deng C., Brown J.A., You D., Brown J.M. Genetics 170:591-600(2005) [PubMed: 15834151] [Abstract] Cited for: FUNCTION.
[20]	"The Saccharomyces cerevisiae Sae2 protein promotes resection and bridging of double strand break ends." Clerici M., Mantiero D., Lucchini G., Longhese M.P. J. Biol. Chem. 280:38631-38638(2005) [PubMed: 16162495] [Abstract] Cited for: FUNCTION.
[21]	"Budding yeast Sae2 is an in vivo target of the Mec1 and Tel1 checkpoint kinases during meiosis." Cartagena-Lirola H., Guerini I., Viscardi V., Lucchini G., Longhese M.P. Cell Cycle 5:1549-1559(2006) [PubMed: 16861895] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION, MUTAGENESIS OF SER-73; THR-90; SER-249; THR-279 AND SER-289.
[22]	"The Saccharomyces cerevisiae Sae2 protein negatively regulates DNA damage checkpoint signalling." Clerici M., Mantiero D., Lucchini G., Longhese M.P. EMBO Rep. 7:212-218(2006) [PubMed: 16374511] [Abstract] Cited for: FUNCTION.
[23]	"Saccharomyces cerevisiae Sae2- and Tel1-dependent single-strand DNA formation at DNA break promotes microhomology-mediated end joining." Lee K., Lee S.E. Genetics 176:2003-2014(2007) [PubMed: 17565964] [Abstract] Cited for: FUNCTION.
[24]	"Examining protein protein interactions using endogenously tagged yeast arrays: the cross-and-capture system." Suter B., Fetchko M.J., Imhof R., Graham C.I., Stoffel-Studer I., Zbinden C., Raghavan M., Lopez L., Beneti L., Hort J., Fillingham J., Greenblatt J.F., Giaever G., Nislow C., Stagljar I. Genome Res. 17:1774-1782(2007) [PubMed: 17989249] [Abstract] Cited for: SUBUNIT, INTERACTION WITH MRE11.
[25]	"Sae2 is an endonuclease that processes hairpin DNA cooperatively with the Mre11/Rad50/Xrs2 complex." Lengsfeld B.M., Rattray A.J., Bhaskara V., Ghirlando R., Paull T.T. Mol. Cell 28:638-651(2007) [PubMed: 18042458] [Abstract] Cited for: FUNCTION, DNA-BINDING, DOMAIN, MUTAGENESIS OF GLY-270.
[26]	"Sae2p phosphorylation is crucial for cooperation with Mre11p for resection of DNA double-strand break ends during meiotic recombination in Saccharomyces cerevisiae." Terasawa M., Ogawa T., Tsukamoto Y., Ogawa H. Genes Genet. Syst. 83:209-217(2008) [PubMed: 18670132] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, MUTAGENESIS OF SER-73; THR-90; SER-249; THR-279 AND SER-289.
[27]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed: 18407956] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-177, MASS SPECTROMETRY.
[28]	"CDK targets Sae2 to control DNA-end resection and homologous recombination." Huertas P., Cortes-Ledesma F., Sartori A.A., Aguilera A., Jackson S.P. Nature 455:689-692(2008) [PubMed: 18716619] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ARG-223; LEU-225 AND SER-267, PHOSPHORYLATION AT SER-267.
[29]	"Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing." Mimitou E.P., Symington L.S. Nature 455:770-774(2008) [PubMed: 18806779] [Abstract] Cited for: FUNCTION.
[30]	"Replicon dynamics, dormant origin firing, and terminal fork integrity after double-strand break formation." Doksani Y., Bermejo R., Fiorani S., Haber J.E., Foiani M. Cell 137:247-258(2009) [PubMed: 19361851] [Abstract] Cited for: FUNCTION.
[31]	"Size-dependent palindrome-induced intrachromosomal recombination in yeast." Lisnic B., Svetec I.K., Stafa A., Zgaga Z. DNA Repair 8:383-389(2009) [PubMed: 19124276] [Abstract] Cited for: FUNCTION.
[32]	"Processing of meiotic DNA double strand breaks requires cyclin-dependent kinase and multiple nucleases." Manfrini N., Guerini I., Citterio A., Lucchini G., Longhese M.P. J. Biol. Chem. 285:11628-11637(2010) [PubMed: 20150422] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF SER-267, PHOSPHORYLATION AT SER-267.
[33]	"A truncated DNA-damage-signaling response is activated after DSB formation in the G1 phase of Saccharomyces cerevisiae." Janke R., Herzberg K., Rolfsmeier M., Mar J., Bashkirov V.I., Haghnazari E., Cantin G., Yates J.R. III, Heyer W.D. Nucleic Acids Res. 38:2302-2313(2010) [PubMed: 20061370] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U49447 Genomic DNA. Translation: AAB96338.1. X84705 Genomic DNA. Translation: CAA59178.1. Z72697 Genomic DNA. Translation: CAA96887.1. BK006941 Genomic DNA. Translation: DAA07938.1.
PIR	S59236.
RefSeq	NP_011340.1. NM_001181040.1.
3D structure databases
ProteinModelPortal	P46946.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-1603N.
IntAct	P46946. 7 interactions.
MINT	MINT-391468.
STRING	P46946.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	YGL175C; YGL175C; YGL175C.
GeneID	852700.
KEGG	sce:YGL175C.
NMPDR	fig\|4932.3.peg.2444.
Organism-specific databases
CYGD	YGL175c.
SGD	S000003143. SAE2.
Phylogenomic databases
eggNOG	fuNOG10983.
OrthoDB	EOG4BK8DJ.
Enzyme and pathway databases
Reactome	REACT_27164. Removal of SPO11 and Resection of 5' Ends of DNA (yeast).
Gene expression databases
ArrayExpress	P46946.
Genevestigator	P46946.
GermOnline	YGL175C. Saccharomyces cerevisiae.
Family and domain databases
ProtoNet	Search...
Other
NextBio	972044.

Entry information

Entry name

COM1_YEAST

Accession

Primary (citable) accession number: P46946
Secondary accession number(s): D6VTX7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	January 25, 2012
This is version 75 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program

Relevant documents

Yeast

Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD

Yeast chromosome VII

Yeast (Saccharomyces cerevisiae) chromosome VII: entries and gene names

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents