Ataxia telangiectasia and Rad3 related
Wikipedia on Answers.com:
Top
Ataxia telangiectasia and Rad3 related
Serine/threonine-protein kinase ATR also known as ataxia telangiectasia and Rad3-related protein (ATR) or FRAP-related protein 1 (FRP1) is an enzyme that in humans is encoded by the ATR gene.[1][2] ATR belongs to the phosphatidylinositol 3-kinase-related kinase protein family.
|
Contents
|
Function
ATR is a serine/threonine-specific protein kinase that is involved in sensing DNA damage and activating the DNA damage checkpoint, leading to cell cycle arrest.[3] ATR is activated in response to persistent single-stranded DNA, which is a common intermediate formed during DNA damage detection and repair. Single-stranded DNA occurs at stalled replication forks and as an intermediate in DNA repair pathways such as nucleotide excision repair and homologous recombination repair. ATR works with a partner protein called ATRIP to recognize single-stranded DNA coated with RPA.[4] Once ATR is activated, it phosphorylates Chk1, initiating a signal transduction cascade that culminates in cell cycle arrest. In addition to its role in activating the DNA damage checkpoint, ATR is thought to function in unperturbed DNA replication.[5]
ATR is related to a second checkpoint-activating kinase, ATM, which is activated by double strand breaks in DNA or chromatin disruption.[6]
Clinical significance
Mutations in ATR are responsible for Seckel syndrome, a rare human disorder that shares some characteristics with ataxia telangiectasia, which results from ATM mutation.[7]
Interactions
Ataxia telangiectasia and Rad3 related has been shown to interact with RAD17,[8][9] Histone deacetylase 2,[10] MSH2,[11] CHD4,[10] BRCA1,[8][12][13][14] P53[8][15] and RHEB.[16]
References
- ^ Cimprich KA, Shin TB, Keith CT, Schreiber SL (April 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. doi:10.1073/pnas.93.7.2850. PMC 39722. PMID 8610130. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=39722.
- ^ Bentley NJ, Holtzman DA, Flaggs G, Keegan KS, DeMaggio A, Ford JC, Hoekstra M, Carr AM (December 1996). "The Schizosaccharomyces pombe rad3 checkpoint gene". EMBO J. 15 (23): 6641–51. PMC 452488. PMID 8978690. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=452488.
- ^ Sancar A, Lindsey-Boltz LA, Unsal-Kaçmaz K, Linn S (2004). "Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints". Annu. Rev. Biochem. 73 (1): 39–85. doi:10.1146/annurev.biochem.73.011303.073723. PMID 15189136.
- ^ Zou L, Elledge SJ (June 2003). "Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes". Science 300 (5625): 1542–8. doi:10.1126/science.1083430. PMID 12791985.
- ^ Brown EJ, Baltimore D (March 2003). "Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance". Genes Dev. 17 (5): 615–28. doi:10.1101/gad.1067403. PMC 196009. PMID 12629044. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=196009.
- ^ Bakkenist CJ, Kastan MB (January 2003). "DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation". Nature 421 (6922): 499–506. doi:10.1038/nature01368. PMID 12556884.
- ^ O'Driscoll M, Ruiz-Perez VL, Woods CG, Jeggo PA, Goodship JA (April 2003). "A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome". Nat. Genet. 33 (4): 497–501. doi:10.1038/ng1129. PMID 12640452.
- ^ a b c Kim, S T; Lim D S, Canman C E, Kastan M B (Dec. 1999). "Substrate specificities and identification of putative substrates of ATM kinase family members". J. Biol. Chem. (UNITED STATES) 274 (53): 37538–43. doi:10.1074/jbc.274.53.37538. ISSN 0021-9258. PMID 10608806.
- ^ Bao, S; Tibbetts R S, Brumbaugh K M, Fang Y, Richardson D A, Ali A, Chen S M, Abraham R T, Wang X F (June 2001). "ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses". Nature (England) 411 (6840): 969–74. doi:10.1038/35082110. ISSN 0028-0836. PMID 11418864.
- ^ a b Schmidt, D R; Schreiber S L (November 1999). "Molecular association between ATR and two components of the nucleosome remodeling and deacetylating complex, HDAC2 and CHD4". Biochemistry (UNITED STATES) 38 (44): 14711–7. doi:10.1021/bi991614n. ISSN 0006-2960. PMID 10545197.
- ^ Wang, Yi; Qin Jun (Dec. 2003). "MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation". Proc. Natl. Acad. Sci. U.S.A. (United States) 100 (26): 15387–92. doi:10.1073/pnas.2536810100. ISSN 0027-8424. PMC 307577. PMID 14657349. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=307577.
- ^ Tibbetts, R S; Cortez D, Brumbaugh K M, Scully R, Livingston D, Elledge S J, Abraham R T (Dec. 2000). "Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress". Genes Dev. (UNITED STATES) 14 (23): 2989–3002. doi:10.1101/gad.851000. ISSN 0890-9369. PMC 317107. PMID 11114888. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=317107.
- ^ Chen, J (September 2000). "Ataxia telangiectasia-related protein is involved in the phosphorylation of BRCA1 following deoxyribonucleic acid damage". Cancer Res. (UNITED STATES) 60 (18): 5037–9. ISSN 0008-5472. PMID 11016625.
- ^ Gatei, M; Zhou B B, Hobson K, Scott S, Young D, Khanna K K (May 2001). "Ataxia telangiectasia mutated (ATM) kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites. In vivo assessment using phospho-specific antibodies". J. Biol. Chem. (United States) 276 (20): 17276–80. doi:10.1074/jbc.M011681200. ISSN 0021-9258. PMID 11278964.
- ^ Fabbro, Megan; Savage Kienan, Hobson Karen, Deans Andrew J, Powell Simon N, McArthur Grant A, Khanna Kum Kum (July 2004). "BRCA1-BARD1 complexes are required for p53Ser-15 phosphorylation and a G1/S arrest following ionizing radiation-induced DNA damage". J. Biol. Chem. (United States) 279 (30): 31251–8. doi:10.1074/jbc.M405372200. ISSN 0021-9258. PMID 15159397.
- ^ Long, Xiaomeng; Lin Yenshou, Ortiz-Vega Sara, Yonezawa Kazuyoshi, Avruch Joseph (April 2005). "Rheb binds and regulates the mTOR kinase". Curr. Biol. (England) 15 (8): 702–13. doi:10.1016/j.cub.2005.02.053. ISSN 0960-9822. PMID 15854902.
Further reading
- Giaccia AJ, Kastan MB (1998). "The complexity of p53 modulation: emerging patterns from divergent signals.". Genes Dev. 12 (19): 2973–83. doi:10.1101/gad.12.19.2973. PMID 9765199.
- Shiloh Y (2001). "ATM and ATR: networking cellular responses to DNA damage.". Curr. Opin. Genet. Dev. 11 (1): 71–7. doi:10.1016/S0959-437X(00)00159-3. PMID 11163154.
- Kastan MB, Lim DS (2001). "The many substrates and functions of ATM.". Nat. Rev. Mol. Cell Biol. 1 (3): 179–86. doi:10.1038/35043058. PMID 11252893.
- Abraham RT (2005). "The ATM-related kinase, hSMG-1, bridges genome and RNA surveillance pathways.". DNA Repair (Amst.) 3 (8-9): 919–25. doi:10.1016/j.dnarep.2004.04.003. PMID 15279777.
- Li L, Li HS, Pauza CD, et al. (2006). "Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions.". Cell Res. 15 (11-12): 923–34. doi:10.1038/sj.cr.7290370. PMID 16354571.
External links
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
 |
This protein-related article is a stub. You can help Wikipedia by expanding it. |
This entry is from Wikipedia, the leading user-contributed encyclopedia. It may not have been reviewed by professional editors (see full disclaimer)
Post a question - any question - to the WikiAnswers community:
Copyrights:
Wikipedia on Answers.com
This article is licensed under the Creative Commons Attribution/Share-Alike License. It uses material from the Wikipedia article Ataxia telangiectasia and Rad3 related.
Read more