MEC1/YBR136W Summary Help

Standard Name MEC1 1
Systematic Name YBR136W
Alias ESR1 2 , SAD3 , RAD31 3
Feature Type ORF, Verified
Description Genome integrity checkpoint protein and PI kinase superfamily member; Mec1p and Dun1p function in same pathway to regulate both dNTP pools and telomere length; signal transducer required for cell cycle arrest and transcriptional responses prompted by damaged or unreplicated DNA; regulates P-body formation induced by replication stress; monitors and participates in meiotic recombination; associates with shortened, dysfunctional telomeres (1, 2, 4, 5, 6, 7, 8, 9, 10 and see Summary Paragraph)
Name Description Mitosis Entry Checkpoint 1
Chromosomal Location
ChrII:505668 to 512774 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All MEC1 GO evidence and references
  View Computational GO annotations for MEC1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulatory Role
Regulatory modules predicted: cellcycle (311)
Mutant phenotypes All MEC1 Phenotype evidence and references
Classical genetics
null
reduction of function
unspecified
Large-scale survey
null
overexpression
Resources
interactions All MEC1 Interaction evidence and references
403 total interaction(s) for 197 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 31
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 17
  • Biochemical Activity: 25
  • Co-localization: 1
  • Reconstituted Complex: 5
  • Two-hybrid: 5
Genetic Interactions
  • Dosage Growth Defect: 4
  • Dosage Lethality: 15
  • Dosage Rescue: 22
  • Negative Genetic: 2
  • Phenotypic Enhancement: 79
  • Phenotypic Suppression: 27
  • Positive Genetic: 1
  • Synthetic Growth Defect: 79
  • Synthetic Lethality: 36
  • Synthetic Rescue: 53
Resources
Expression Summary
histogram
Resources
Protein Information All MEC1 Protein evidence and references
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrII:505668 to 512774 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1997-01-28
Subfeature details
Relative
Coordinates		 Chromosomal
Coordinates		 Most Recent Updates
Coordinates Sequence
CDS 1..7107 505668..512774 2011-02-03 1997-01-28
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000000340
SUMMARY PARAGRAPH for MEC1

MEC1 encodes an essential phosphoinositide (PI)-3-kinase-related protein kinase required for cell cycle checkpoint function (1, 2). By modifying the phosphorylation state of other proteins, Mec1p initiates a signal transduction cascade in response to DNA damage and replication blocks (reviewed in 6 and 11). In addition to its checkpoint function, Mec1p has been shown to preferentially bind shortened telomeres, to act as a sensor for telomere abnormalities, and to be necessary for telomere silencing (12, 13).

Mec1p-dependent signaling begins with phosphorylation of Rad9p (14, 15). Activated Rad9p amplifies this initial signal by stimulating Mec1p phosphorylation of the effector kinases Chk1p and Rad53p (16, 17, 18). Chk1p and Rad53p phosphorylation leads to the arrest of cells in G1/S, intra-S, or G2/M phase, as well as the transcriptional upregulation of DNA damage repair genes, transcriptional repression of cyclins, and stabilization of replication forks (reviewed in 19 and 7). Other direct targets of Mec1p include the single-stranded DNA binding protein replication protein A (RPA) and Esc4p, which is required for stalled replication forks to resume activity (20, 21, 22).

Mec1p forms a complex with Lcd1p that binds to damaged DNA in a reciprocally-dependant manner (23, 24). Lcd1p is also necessary for Mec1p to associate with telomeres (12). The presence of Mec1p is required for Rad9p to associate with DNA damage sites (14). In addition, Rad9p has been shown to play a role in regulating MEC1 expression (18, 25).

Mutations in MEC1 lead to multiple defects, including sensitivity to DNA damaging agents, impaired checkpoint functions, chromosome breakage, and loss of telomeric silencing (2, 1, 26, 13). MEC1 is the homolog of S. pombe RAD3 and human ATR (OMIM; 2, 27). Mutations in ATR have been associated with the autosomal recessive disorder Seckel Syndrome 1, which is characterized by mental retardation, growth retardation, and microcephaly (OMIM; 28).

Last updated: 2006-03-24

References cited on this page View Complete Literature Guide for MEC1
1) Weinert TA, et al.  (1994) Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair. Genes Dev 8(6):652-65
2) Kato R and Ogawa H  (1994) An essential gene, ESR1, is required for mitotic cell growth, DNA repair and meiotic recombination in Saccharomyces cerevisiae. Nucleic Acids Res 22(15):3104-12
3) Kozhina TN, et al.  (2011) [Gene RAD31 is identical to gene MEC1 of yeast Saccharomyces cerevisiae]. Genetika 47(5):610-4
4) Grushcow JM, et al.  (1999) Saccharomyces cerevisiae checkpoint genes MEC1, RAD17 and RAD24 are required for normal meiotic recombination partner choice. Genetics 153(2):607-20
5) Kiser GL and Weinert TA  (1996) Distinct roles of yeast MEC and RAD checkpoint genes in transcriptional induction after DNA damage and implications for function. Mol Biol Cell 7(5):703-18
6) Elledge SJ  (1996) Cell cycle checkpoints: preventing an identity crisis. Science 274(5293):1664-72
7) Weinert T  (1998) DNA damage checkpoints update: getting molecular. Curr Opin Genet Dev 8(2):185-93
8) Hector RE, et al.  (2012) Mec1p associates with functionally compromised telomeres. Chromosoma 121(3):277-90
9) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
10) Gupta A, et al.  (2013) Telomere Length Homeostasis Responds to Changes in Intracellular dNTP Pools. Genetics 193(4):1095-105
11) Carr AM  (1997) Control of cell cycle arrest by the Mec1sc/Rad3sp DNA structure checkpoint pathway. Curr Opin Genet Dev 7(1):93-8
12) Takata H, et al.  (2004) Reciprocal association of the budding yeast ATM-related proteins Tel1 and Mec1 with telomeres in vivo. Mol Cell 14(4):515-22
13) Craven RJ and Petes TD  (2000) Involvement of the checkpoint protein Mec1p in silencing of gene expression at telomeres in Saccharomyces cerevisiae. Mol Cell Biol 20(7):2378-84
14) Naiki T, et al.  (2004) Association of Rad9 with double-strand breaks through a Mec1-dependent mechanism. Mol Cell Biol 24(8):3277-85
15) Emili A  (1998) MEC1-dependent phosphorylation of Rad9p in response to DNA damage. Mol Cell 2(2):183-9
16) Blankley RT and Lydall D  (2004) A domain of Rad9 specifically required for activation of Chk1 in budding yeast. J Cell Sci 117(Pt 4):601-8
17) Ma JL, et al.  (2006) Activation of the checkpoint kinase Rad53 by the phosphatidyl inositol kinase-like kinase Mec1. J Biol Chem 281(7):3954-63
18) Sweeney FD, et al.  (2005) Saccharomyces cerevisiae Rad9 acts as a Mec1 adaptor to allow Rad53 activation. Curr Biol 15(15):1364-75
19) Chen Y and Sanchez Y  (2004) Chk1 in the DNA damage response: conserved roles from yeasts to mammals. DNA Repair (Amst) 3(8-9):1025-32
20) Kim HS and Brill SJ  (2003) MEC1-dependent phosphorylation of yeast RPA1 in vitro. DNA Repair (Amst) 2(12):1321-35
21) Bartrand AJ, et al.  (2004) DNA stimulates Mec1-mediated phosphorylation of replication protein A. J Biol Chem 279(25):26762-7
22) Rouse J  (2004) Esc4p, a new target of Mec1p (ATR), promotes resumption of DNA synthesis after DNA damage. EMBO J 23(5):1188-97
23) Nakada D, et al.  (2005) Role of the C terminus of Mec1 checkpoint kinase in its localization to sites of DNA damage. Mol Biol Cell 16(11):5227-35
24) Rouse J and Jackson SP  (2002) Lcd1p recruits Mec1p to DNA lesions in vitro and in vivo. Mol Cell 9(4):857-69
25) Aboussekhra A, et al.  (1996) A novel role for the budding yeast RAD9 checkpoint gene in DNA damage-dependent transcription. EMBO J 15(15):3912-22
26) Cha RS and Kleckner N  (2002) ATR homolog Mec1 promotes fork progression, thus averting breaks in replication slow zones. Science 297(5581):602-6
27) Cimprich KA, et al.  (1996) cDNA cloning and gene mapping of a candidate human cell cycle checkpoint protein. Proc Natl Acad Sci U S A 93(7):2850-5
28) O'Driscoll M, et al.  (2003) A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. Nat Genet 33(4):497-501