RAD24/YER173W Summary Help

Standard Name RAD24 1
Systematic Name YER173W
Feature Type ORF, Verified
Description Checkpoint protein; involved in the activation of the DNA damage and meiotic pachytene checkpoints; subunit of a clamp loader that loads Rad17p-Mec3p-Ddc1p onto DNA; homolog of human and S. pombe Rad17 protein (2, 3, 4 and see Summary Paragraph)
Also known as: RS1
Name Description RADiation sensitive
Chromosomal Location
ChrV:536300 to 538279 | ORF Map | GBrowse
Gbrowse
Genetic position: 147 cM
Gene Ontology Annotations All RAD24 GO evidence and references
  View Computational GO annotations for RAD24
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 69 genes
Resources
Classical genetics
null
Large-scale survey
null
Resources
323 total interaction(s) for 152 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 10
  • Affinity Capture-Western: 15
  • Biochemical Activity: 1
  • Co-fractionation: 1
  • Co-localization: 1
  • Co-purification: 4
  • Reconstituted Complex: 8
  • Two-hybrid: 6

Genetic Interactions
  • Dosage Growth Defect: 2
  • Dosage Lethality: 9
  • Dosage Rescue: 5
  • Negative Genetic: 73
  • Phenotypic Enhancement: 37
  • Phenotypic Suppression: 26
  • Positive Genetic: 3
  • Synthetic Growth Defect: 70
  • Synthetic Lethality: 25
  • Synthetic Rescue: 27

Resources
Expression Summary
histogram
Resources
Length (a.a.) 659
Molecular Weight (Da) 75,726
Isoelectric Point (pI) 6.35
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrV:536300 to 538279 | ORF Map | GBrowse
SGD ORF map
Genetic position: 147 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1980 536300..538279 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000000975
SUMMARY PARAGRAPH for RAD24

S. cerevisiae contains four structurally related complexes known as Replication Factor C (RFC) complexes, which are involved in various aspects of DNA metabolism. These complexes are comprised of 4 small subunits (Rfc2p/Rfc3p/Rfc4p/Rfc5p) and a large subunit whose identity varies depending on the process (5 and references therein). The alternate forms of the large subunit and their pathway roles include: Rfc1p during processive DNA synthesis, Ctf18p during sister chromatid cohesion (6), Elg1p for genomic stability (7), and Rad24p during DNA damage checkpoints (8).

Rad24-RFC, which contains Rad24p, Rfc2p, Rfc3p, Rfc4p, and Rfc5p, (also known as Rad17-RFC in other organisms) is a checkpoint complex that functions to load the PCNA-like clamp Rad17p/Mec3p/Ddc1p (the equivalent of the human 9-1-1 complex) onto DNA (3). Checkpoints are regulatory signal transduction cascades that are triggered by incompletely replicated or damaged chromsomes that lead to cell cycle arrest and DNA repair. The Rad24-RFC complex is involved in both mitotic checkpoints for repair of double-strand breaks (at G1, S, and G2/M; 9, 10, 11, 12, 13) and meiotic checkpoints that monitor meiotic recombination (2, 14, 15, 4). The RAD24 pathway is one of two DNA damage checkpoint pathways, the other involving the RAD9 epistasis group, that converge on Rad53p phosphorylation (16, 17). The ATP-binding activity of Rad24p is necessary for the ATPase and clamp loading activities of the RFC complex (18, 3). Rad24-RFC interaction with DNA during clamp loading is mediated through interactions with Replication protein A (19). Rad24p is phosphorylated by the checkpoint kinase Mec1p (20).

Rad24p is also involved in processing double-strand break ends and recombination partner choice (21), efficient inducible nucleotide excision repair and non-homologous end joining (22, 23), and telomere maintenance through stimulation of Ty1 transposition (24, 25, 26, 27). Cells lacking Rad24p function are impaired at the various DNA damage checkpoints (28, 4), show decreased stability at CAG expansion sites (29), produce inviable spores, and are delayed entering into meiosis I (4).

RAD24 is the homolog of S. pombe rad17 and human HRad17 (30, 31). Overexpression of HRad17 has been associated with human breast and colon cancers (32, 33).

Last updated: 2010-05-14 Contact SGD

References cited on this page View Complete Literature Guide for RAD24
1) Eckardt, F. and Game, J.  (1985) Personal Communication, Mortimer Map Edition 9
2) Lydall D, et al.  (1996) A meiotic recombination checkpoint controlled by mitotic checkpoint genes. Nature 383(6603):840-3
3) Majka J and Burgers PM  (2003) Yeast Rad17/Mec3/Ddc1: a sliding clamp for the DNA damage checkpoint. Proc Natl Acad Sci U S A 100(5):2249-54
4) Shinohara M, et al.  (2003) The mitotic DNA damage checkpoint proteins Rad17 and Rad24 are required for repair of double-strand breaks during meiosis in yeast. Genetics 164(3):855-65
5) Bylund GO, et al.  (2006) Overproduction and purification of RFC-related clamp loaders and PCNA-related clamps from Saccharomyces cerevisiae. Methods Enzymol 409():1-11
6) Naiki T, et al.  (2001) Chl12 (Ctf18) forms a novel replication factor C-related complex and functions redundantly with Rad24 in the DNA replication checkpoint pathway. Mol Cell Biol 21(17):5838-45
7) Ben-Aroya S, et al.  (2003) ELG1, a yeast gene required for genome stability, forms a complex related to replication factor C. Proc Natl Acad Sci U S A 100(17):9906-11
8) Green CM, et al.  (2000) A novel Rad24 checkpoint protein complex closely related to replication factor C. Curr Biol 10(1):39-42
9) Siede W, et al.  (1994) Characterization of G1 checkpoint control in the yeast Saccharomyces cerevisiae following exposure to DNA-damaging agents. Genetics 138(2):271-81
10) Paulovich AG, et al.  (1997) RAD9, RAD17, and RAD24 are required for S phase regulation in Saccharomyces cerevisiae in response to DNA damage. Genetics 145(1):45-62
11) King WR, et al.  (2003) Ionizing irradiation effects on S-phase in checkpoint mutants of the yeast Saccharomyces cerevisiae. Curr Genet 42(6):313-21
12) Weinert TA  (1992) Dual cell cycle checkpoints sensitive to chromosome replication and DNA damage in the budding yeast Saccharomyces cerevisiae. Radiat Res 132(2):141-3
13) 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
14) Thompson DA and Stahl FW  (1999) Genetic control of recombination partner preference in yeast meiosis. Isolation and characterization of mutants elevated for meiotic unequal sister-chromatid recombination. Genetics 153(2):621-41
15) 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
16) de la Torre-Ruiz MA, et al.  (1998) RAD9 and RAD24 define two additive, interacting branches of the DNA damage checkpoint pathway in budding yeast normally required for Rad53 modification and activation. EMBO J 17(9):2687-98
17) Pellicioli A, et al.  (1999) Activation of Rad53 kinase in response to DNA damage and its effect in modulating phosphorylation of the lagging strand DNA polymerase. EMBO J 18(22):6561-72
18) Majka J, et al.  (2004) Requirement for ATP by the DNA damage checkpoint clamp loader. J Biol Chem 279(20):20921-6
19) Majka J, et al.  (2006) Replication protein A directs loading of the DNA damage checkpoint clamp to 5'-DNA junctions. J Biol Chem 281(38):27855-61
20) Majka J, et al.  (2006) The checkpoint clamp activates Mec1 kinase during initiation of the DNA damage checkpoint. Mol Cell 24(6):891-901
21) Aylon Y and Kupiec M  (2003) The checkpoint protein Rad24 of Saccharomyces cerevisiae is involved in processing double-strand break ends and in recombination partner choice. Mol Cell Biol 23(18):6585-96
22) Yu S, et al.  (2001) RAD9, RAD24, RAD16 and RAD26 are required for the inducible nucleotide excision repair of UV-induced cyclobutane pyrimidine dimers from the transcribed and non-transcribed regions of the Saccharomyces cerevisiae MFA2 gene. Mutat Res 485(3):229-36
23) de la Torre-Ruiz M and Lowndes NF  (2000) The Saccharomyces cerevisiae DNA damage checkpoint is required for efficient repair of double strand breaks by non-homologous end joining. FEBS Lett 467(2-3):311-5
24) Scholes DT, et al.  (2003) Activation of a LTR-retrotransposon by telomere erosion. Proc Natl Acad Sci U S A 100(26):15736-41
25) Zubko MK, et al.  (2004) Exo1 and Rad24 differentially regulate generation of ssDNA at telomeres of Saccharomyces cerevisiae cdc13-1 mutants. Genetics 168(1):103-15
26) Grandin N and Charbonneau M  (2007) Control of the yeast telomeric senescence survival pathways of recombination by the Mec1 and Mec3 DNA damage sensors and RPA. Nucleic Acids Res 35(3):822-38
27) Curcio MJ, et al.  (2007) S-phase checkpoint pathways stimulate the mobility of the retrovirus-like transposon Ty1. Mol Cell Biol 27(24):8874-85
28) Kondo T, et al.  (1999) Role of a complex containing Rad17, Mec3, and Ddc1 in the yeast DNA damage checkpoint pathway. Mol Cell Biol 19(2):1136-43
29) Lahiri M, et al.  (2004) Expanded CAG repeats activate the DNA damage checkpoint pathway. Mol Cell 15(2):287-93
30) Griffiths DJ, et al.  (1995) Fission yeast rad17: a homologue of budding yeast RAD24 that shares regions of sequence similarity with DNA polymerase accessory proteins. EMBO J 14(23):5812-23
31) Bluyssen HA, et al.  (1999) Human and mouse homologs of the Schizosaccharomyces pombe rad17+ cell cycle checkpoint control gene. Genomics 55(2):219-28
32) Bao S, et al.  (1999) HRad17, a human homologue of the Schizosaccharomyces pombe checkpoint gene rad17, is overexpressed in colon carcinoma. Cancer Res 59(9):2023-8
33) Kataoka A, et al.  (2001) Overexpression of HRad17 mRNA in human breast cancer: correlation with lymph node metastasis. Clin Cancer Res 7(9):2815-20