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Mec1p

Protein FULL name:

Genome integrity checkpoint protein and PI kinase superfamily member; signal transducer required for cell cycle arrest and transcriptional responses prompted by damaged or unreplicated DNA; monitors and participates in meiotic recombination


Mec1p (Saccharomyces cerevisiae) is product of expression of MEC1 gene.


Mec1p is involved in:

DDS in Saccharomyces cerevisiae
     


Keywords:



FUNCTION: Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Recruited in complex with protein LCD1 by the single-strand-binding protein complex RPA to DNA lesions in order to initiate the DNA repair by homologous recombination, after the MRX-complex and TEL1 are displaced. Phosphorylates LCD1 and RPA2, a subunit of RPA, involved in DNA replication, repair and recombination. Phosphorylates RAD9, CHK1 and RAD53, which leads to the activation of the CHK1 and RAD53 kinases involved in DNA damage repair cascade. Phosphorylates histone H2A to form H2AS128ph (gamma-H2A) at sites of DNA damage, also involved in the regulation of DNA damage response mechanism. Phosphorylates also SLX4 and RTT107 which are proteins involved in genome stability. Required for cell growth and meiotic recombination.

CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.

SUBUNIT: Interacts with LCD1, which is required for localization MEC1 to the RPA complex. Interacts directly with the RPA subunits RFA1 and RFA2.

INTERACTION: Q04377:LCD1; NbExp=4; IntAct=EBI-6668, EBI-35652; P34217:PIN4; NbExp=1; IntAct=EBI-6668, EBI-21256;

SUBCELLULAR LOCATION: Nucleus. Note=Localizes to nuclear DNA repair foci in response to DNA double strand breaks. The recruitment to DNA lesion sites requires its interaction with LCD1 and the presence of the RPA complex on DNA.

DEVELOPMENTAL STAGE: Induced during meiosis.

SIMILARITY: Belongs to the PI3/PI4-kinase family. ATM subfamily.

SIMILARITY: Contains 1 FAT domain.

SIMILARITY: Contains 1 FATC domain.

SIMILARITY: Contains 5 HEAT repeats.

SIMILARITY: Contains 1 PI3K/PI4K domain.


NCBI GenPept GI number(s): 6319612
Species: Saccharomyces cerevisiae

Links to other databases:

Database ID Link
Uniprot P38111 P38111
PFAM: - P38111 (Link - using uniprot id)
InterPro: - P38111 (Link - using uniprot id)
CATH: - -
SCOP: - -
PDB: - -


Protein sequence:
MESHVKYLDELILAIKDLNSGVDSKVQIKKVPTDPSSSQEYAKSLKILNT
LIRNLKDQRRNNIMKNDTIFSKTVSALALLLEYNPFLLVMKDSNGNFEIQ
RLIDDFLNISVLNYDNYHRIWFMRRKLGSWCKACVEFYGKPAKFQLTAHF
ENTMNLYEQALTEVLLGKTELLKFYDTLKGLYILLYWFTSEYSTFGNSIA
FLDSSLGFTKFDFNFQRLIRIVLYVFDSCELAALEYAEIQLKYISLVVDY
VCNRTISTALDAPALVCCEQLKFVLTTMHHFLDNKYGLLDNDPTMAKGIL
RLYSLCISNDFSKCFVDHFPIDQWADFSQSEHFPFTQLTNKALSIVYFDL
KRRSLPVEALKYDNKFNIWVYQSEPDSSLKNVTSPFDDRYKQLEKLRLLV
LKKFNKTERGTLLKYRVNQLSPGFFQRAGNDFKLILNEASVSIQTCFKTN
NITRLTSWTVILGRLACLESEKFSGTLPNSTKDMDNWYVCHLCDIEKTGN
PFVRINPNRPEAAGKSEIFRILHSNFLSHPNIDEFSESLLSGILFSLHRI
FSHFQPPKLTDGNGQINKSFKLVQKCFMNSNRYLRLLSTRIIPLFNISDS
HNSEDEHTATLIKFLQSQKLPVVKENLVIAWTQLTLTTSNDVFDTLLLKL
IDIFNSDDYSLRIMMTLQIKNMAKILKKTPYQLLSPILPVLLRQLGKNLV
ERKVGFQNLIELLGYSSKTILDIFQRYIIPYAIIQYKSDVLSEIAKIMCD
GDTSLINQMKVNLLKKNSRQIFAVALVKHGLFSLDILETLFLNRAPTFDK
GYITAYLPDYKTLAEITKLYKNSVTKDASDSENANMILCSLRFLITNFEK
DKRHGSKYKNINNWTDDQEQAFQKKLQDNILGIFQVFSSDIHDVEGRTTY
YEKLRVINGISFLIIYAPKKSIISALAQISICLQTGLGLKEVRYEAFRCW
HLLVRHLNDEELSTVIDSLIAFILQKWSEFNGKLRNIVYSILDTLIKEKS
DLILKLKPYTTLALVGKPELGILARDGQFARMVNKIRSTTDLIPIFANNL
KSSNKYVINQNLDDIEVYLRRKQTERSIDFTPKKVGQTSDITLVLGALLD
TSHKFRNLDKDLCEKCAKCISMIGVLDVTKHEFKRTTYSENEVYDLNDSV
QTIKFLIWVINDILVPAFWQSENPSKQLFVALVIQESLKYCGLSSESWDM
NHKELYPNEAKLWEKFNSVSKTTIYPLLSSLYLAQSWKEYVPLKYPSNNF
KEGYKIWVKRFTLDLLKTGTTENHPLHVFSSLIREDDGSLSNFLLPYISL
DIIIKAEKGTPYADILNGIIIEFDSIFTCNLEGMNNLQVDSLRMCYESIF
RVFEYCKKWATEFKQNYSKLHGTFIIKDTKTTNMLLRIDEFLRTTPSDLL
AQRSLETDSFERSALYLEQCYRQNPHDKNQNGQLLKNLQITYEEIGDIDS
LDGVLRTFATGNLVSKIEELQYSENWKLAQDCFNVLGKFSDDPKTTTRML
KSMYDHQLYSQIISNSSFHSSDGKISLSPDVKEWYSIGLEAANLEGNVQT
LKNWVEQIESLRNIDDREVLLQYNIAKALIAISNEDPLRTQKYIHNSFRL
IGTNFITSSKETTLLKKQNLLMKLHSLYDLSFLSSAKDKFEYKSNTTILD
YRMERIGADFVPNHYILSMRKSFDQLKMNEQADADLGKTFFTLAQLARNN
ARLDIASESLMHCLERRLPQAELEFAEILWKQGENDRALKIVQEIHEKYQ
ENSSVNARDRAAVLLKFTEWLDLSNNSASEQIIKQYQDIFQIDSKWDKPY
YSIGLYYSRLLERKKAEGYITNGRFEYRAISYFLLAFEKNTAKVRENLPK
VITFWLDIAAASISEAPGNRKEMLSKATEDICSHVEEALQHCPTYIWYFV
LTQLLSRLLHSHQSSAQIIMHILLSLAVEYPSHILWYITALVNSNSSKRV
LRGKHILEKYRQHSQNPHDLVSSALDLTKALTRVCLQDVKSITSRSGKSL
EKDFKFDMNVAPSAMVVPVRKNLDIISPLESNSMRGYQPFRPVVSIIRFG
SSYKVFSSLKKPKQLNIIGSDGNIYGIMCKKEDVRQDNQYMQFATTMDFL
LSKDIASRKRSLGINIYSVLSLREDCGILEMVPNVVTLRSILSTKYESLK
IKYSLKSLHDRWQHTAVDGKLEFYMEQVDKFPPILYQWFLENFPDPINWF
NARNTYARSYAVMAMVGHILGLGDRHCENILLDIQTGKVLHVDFDCLFEK
GKRLPVPEIVPFRLTPNLLDALGIIGTEGTFKKSSEVTLALMRKNEVALM
NVIETIMYDRNMDHSIQKALKVLRNKIRGIDPQDGLVLSVAGQTETLIQE
ATSEDNLSKMYIGWLPFW

Mec1p (Saccharomyces cerevisiae) belongs to following protein families:
References:

Title Authors Journal
Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair. Weinert TA, Kiser GL, Hartwell LH Genes Dev March 15, 1994
The sequence of 29.7 kb from the right arm of chromosome II reveals 13 complete open reading frames, of which ten correspond to new genes. Becam AM, Cullin C, Grzybowska E, Lacroute F, Nasr F, Ozier-Kalogeropoulos O, Palucha A, Slonimski PP, Zagulski M, Herbert CJ Yeast April 1, 1994
An essential gene, ESR1, is required for mitotic cell growth, DNA repair and meiotic recombination in Saccharomyces cerevisiae. Kato R, Ogawa H Nucleic Acids Res Aug. 11, 1994
Complete DNA sequence of yeast chromosome II. Feldmann H, Aigle M, Aljinovic G, Andre B, Baclet MC, Barthe C, Baur A, Becam AM, Biteau N, Boles E, et al. EMBO J Dec. 15, 1994
Regulation of RAD53 by the ATM-like kinases MEC1 and TEL1 in yeast cell cycle checkpoint pathways. Sanchez Y, Desany BA, Jones WJ, Liu Q, Wang B, Elledge SJ Science Feb. 19, 1996
The ATM homologue MEC1 is required for phosphorylation of replication protein A in yeast. Brush GS, Morrow DM, Hieter P, Kelly TJ Proc Natl Acad Sci U S A Dec. 24, 1996
A role for Saccharomyces cerevisiae histone H2A in DNA repair. Downs JA, Lowndes NF, Jackson SP Nature Jan. 1, 2000
The checkpoint protein Ddc2, functionally related to S. pombe Rad26, interacts with Mec1 and is regulated by Mec1-dependent phosphorylation in budding yeast. Paciotti V, Clerici M, Lucchini G, Longhese MP Genes Dev Aug. 15, 2000
LCD1: an essential gene involved in checkpoint control and regulation of the MEC1 signalling pathway in Saccharomyces cerevisiae. Rouse J, Jackson SP EMBO J Nov. 1, 2000
Protein kinase activity of Tel1p and Mec1p, two Saccharomyces cerevisiae proteins related to the human ATM protein kinase. Mallory JC, Petes TD Proc Natl Acad Sci U S A Dec. 5, 2000
Characterization of mec1 kinase-deficient mutants and of new hypomorphic mec1 alleles impairing subsets of the DNA damage response pathway. Paciotti V, Clerici M, Scotti M, Lucchini G, Longhese MP Mol Cell Biol June 1, 2001
MEC3, MEC1, and DDC2 are essential components of a telomere checkpoint pathway required for cell cycle arrest during senescence in Saccharomyces cerevisiae. Enomoto S, Glowczewski L, Berman J Mol Biol Cell Aug. 1, 2002
Yeast histone 2A serine 129 is essential for the efficient repair of checkpoint-blind DNA damage. Redon C, Pilch DR, Rogakou EP, Orr AH, Lowndes NF, Bonner WM EMBO Rep July 1, 2003
Esc4p, a new target of Mec1p (ATR), promotes resumption of DNA synthesis after DNA damage. Rouse J EMBO J March 10, 2004
Choreography of the DNA damage response: spatiotemporal relationships among checkpoint and repair proteins. Lisby M, Barlow JH, Burgess RC, Rothstein R Cell Sept. 17, 2004
Distribution and dynamics of chromatin modification induced by a defined DNA double-strand break. Shroff R, Arbel-Eden A, Pilch D, Ira G, Bonner WM, Petrini JH, Haber JE, Lichten M Curr Biol Oct. 5, 2004
Slx4 becomes phosphorylated after DNA damage in a Mec1/Tel1-dependent manner and is required for repair of DNA alkylation damage. Flott S, Rouse J Biochem J Oct. 15, 2005
Role of the C terminus of Mec1 checkpoint kinase in its localization to sites of DNA damage. Nakada D, Hirano Y, Tanaka Y, Sugimoto K Mol Biol Cell Nov. 1, 2005
Activation of the checkpoint kinase Rad53 by the phosphatidyl inositol kinase-like kinase Mec1. Ma JL, Lee SJ, Duong JK, Stern DF J Biol Chem Jan. 17, 2006
Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases. Smolka MB, Albuquerque CP, Chen SH, Zhou H Proc Natl Acad Sci U S A June 19, 2007
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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