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RAD50

RAD50 homolog (S. cerevisiae)

Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11A. RAD50 may be required to bind DNA ends and hold them in close proximity. This could facilitate searches for short or long regions of sequence homology in the recombining DNA templates, and may also stimulate the activity of DNA ligases and/or restrict the nuclease activity of MRE11A to prevent nucleolytic degradation past a given point. The complex may also be required for DNA damage signaling via activation of the ATM kinase. In telomeres the MRN complex may modulate t-loop formation.

Gene Name:	RAD50 homolog (S. cerevisiae)
Synonyms:	RAD50, DNA repair protein RAD50, HRad50, NBSLD, RAD50 (S. cerevisiae) homolog, RAD50 homolog (S. cerevisiae), RAD502, RAD50-2
Target Sequences:	NM_005732 NP_005723.2 Q92878

Publications (25)

Human MRE11 is inactivated in mismatch repair-deficient cancers. Giannini G, Ristori E, Cerignoli F, Rinaldi C, Zani M, Viel A, Ottini L, Crescenzi M, Martinotti S, Bignami M, Frati L, Screpanti I, Gulino A. EMBO reports. 2002 3:248-54. [PubMed:11850399] [PMC:PMC1084012]

Phosphorylation of histone H2AX and activation of Mre11, Rad50, and Nbs1 in response to replication-dependent DNA double-strand breaks induced by mammalian DNA topoisomerase I cleavage complexes. Furuta T, Takemura H, Liao ZY, Aune GJ, Redon C, Sedelnikova OA, Pilch DR, Rogakou EP, Celeste A, Chen HT, Nussenzweig A, Aladjem MI, Bonner WM, Pommier Y. The Journal of biological chemistry. 2003 278:20303-12. (WB; Human) [PubMed:12660252]

Telomere maintenance and cell cycle regulation in spontaneously immortalized T-cell lines from Nijmegen breakage syndrome patients. Siwicki JK, Degerman S, Chrzanowska KH, Roos G. Experimental cell research. 2003 287:178-89. (WB, IP, Flo; Human) [PubMed:12799193]

Distinct pathways of nonhomologous end joining that are differentially regulated by DNA-dependent protein kinase-mediated phosphorylation. Udayakumar D, Bladen CL, Hudson FZ, Dynan WS. The Journal of biological chemistry. 2003 278:41631-5. (WB; Human) [PubMed:12917393]

Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks. Sedelnikova OA, Horikawa I, Zimonjic DB, Popescu NC, Bonner WM, Barrett JC. Nature cell biology. 2004 6:168-70. (Mouse) [PubMed:14755273]

Linkage between Werner syndrome protein and the Mre11 complex via Nbs1. Cheng WH, von Kobbe C, Opresko PL, Arthur LM, Komatsu K, Seidman MM, Carney JP, Bohr VA. The Journal of biological chemistry. 2004 279:21169-76. (ICC, WB, IP; Human) [PubMed:15026416]

Independent roles for nibrin and Mre11-Rad50 in the activation and function of Atm. Cerosaletti K, Concannon P. The Journal of biological chemistry. 2004 279:38813-9. (ICC, WB; Human) [PubMed:15234984]

Defective DNA strand break repair after DNA damage in prostate cancer cells: implications for genetic instability and prostate cancer progression. Fan R, Kumaravel TS, Jalali F, Marrano P, Squire JA, Bristow RG. Cancer research. 2004 64:8526-33. [PubMed:15574758]

Mdm2 binds to Nbs1 at sites of DNA damage and regulates double strand break repair. Alt JR, Bouska A, Fernandez MR, Cerny RL, Xiao H, Eischen CM. The Journal of biological chemistry. 2005 280:18771-81. (ICC, WB; Human) [PubMed:15734743]

Active role for nibrin in the kinetics of atm activation. Cerosaletti K, Wright J, Concannon P. Molecular and cellular biology. 2006 26:1691-9. [PubMed:16478990] [PMC:PMC1430256]

The Rb-related p130 protein controls telomere lengthening through an interaction with a Rad50-interacting protein, RINT-1. Kong LJ, Meloni AR, Nevins JR. Molecular cell. 2006 22:63-71. [PubMed:16600870]

Mre11-Rad50-Nbs1 complex is activated by hypertonicity. Sheen MR, Kim SW, Jung JY, Ahn JY, Rhee JG, Kwon HM, Woo SK. American journal of physiology. Renal physiology. 2006 291:F1014-20. [PubMed:16788144]

Defective Mre11-dependent activation of Chk2 by ataxia telangiectasia mutated in colorectal carcinoma cells in response to replication-dependent DNA double strand breaks. Takemura H, Rao VA, Sordet O, Furuta T, Miao ZH, Meng L, Zhang H, Pommier Y. The Journal of biological chemistry. 2006 281:30814-23. [PubMed:16905549]

Dimerization of the Rad50 protein is independent of the conserved hook domain. Cahill D, Carney JP. Mutagenesis. 2007 22:269-74. [PubMed:17426050]

DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models. Sedelnikova OA, Nakamura A, Kovalchuk O, Koturbash I, Mitchell SA, Marino SA, Brenner DJ, Bonner WM. Cancer research. 2007 67:4295-302. [PubMed:17483342]

RIDDLE immunodeficiency syndrome is linked to defects in 53BP1-mediated DNA damage signaling. Stewart GS, Stankovic T, Byrd PJ, Wechsler T, Miller ES, Huissoon A, Drayson MT, West SC, Elledge SJ, Taylor AM. Proceedings of the National Academy of Sciences of the United States of America. 2007 104:16910-5. [PubMed:17940005] [PMC:PMC2040433]

Chronic hypoxia decreases synthesis of homologous recombination proteins to offset chemoresistance and radioresistance. Chan N, Koritzinsky M, Zhao H, Bindra R, Glazer PM, Powell S, Belmaaza A, Wouters B, Bristow RG. Cancer research. 2008 68:605-14. [PubMed:18199558]

A glycine-arginine domain in control of the human MRE11 DNA repair protein. Dry U, Coulombe Y, Rodrigue A, Stasiak A, Richard S, Masson JY. Molecular and cellular biology. 2008 28:3058-69. [PubMed:18285453] [PMC:PMC2293076]

Mdm2 promotes genetic instability and transformation independent of p53. Bouska A, Lushnikova T, Plaza S, Eischen CM. Molecular and cellular biology. 2008 28:4862-74. [PubMed:18541670] [PMC:PMC2493369]

Temporal regulation of the Mre11-Rad50-Nbs1 complex during adenovirus infection. Karen KA, Hoey PJ, Young CS, Hearing P. Journal of virology. 2009 83:4565-73. [PubMed:19244322] [PMC:PMC2668508]

Rad50 zinc hook is important for the Mre11 complex to bind chromosomal DNA double-stranded breaks and initiate various DNA damage responses. He J, Shi LZ, Truong LN, Lu CS, Razavian N, Li Y, Negrete A, Shiloach J, Berns MW, Wu X. The Journal of biological chemistry. 2012 287:31747-56. (WB; Human) [PubMed:22833675] [PMC:PMC3442509]

The Mre11 nuclease is critical for the sensitivity of cells to Chk1 inhibition. Thompson R, Montano R, Eastman A. PloS one. 2012 7:e44021. (WB; Human) [PubMed:22937147] [PMC:PMC3427249]

PALB2 self-interaction controls homologous recombination. Buisson R, Masson JY. Nucleic acids research. 2012 40:10312-23. (Human) [PubMed:22941656] [PMC:PMC3488246]

The RING finger protein RNF8 ubiquitinates Nbs1 to promote DNA double-strand break repair by homologous recombination. Lu CS, Truong LN, Aslanian A, Shi LZ, Li Y, Hwang PY, Koh KH, Hunter T, Yates JR, Berns MW, Wu X. The Journal of biological chemistry. 2012 287:43984-94. (WB, IP; Human) [PubMed:23115235] [PMC:PMC3527981]

Mitochondrial dysfunction in a novel form of autosomal recessive ataxia. Murad NA, Cullen JK, McKenzie M, Ryan MT, Thorburn D, Gueven N, Kobayashi J, Birrell G, Yang J, Drk T, Becherel O, Grattan-Smith P, Lavin MF. Mitochondrion. 2013 13:235-45. (WB; Human) [PubMed:23178371]

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For RESEARCH USE ONLY. Intended for use by laboratory professionals. Not intended for human diagnostic or therapeutic purposes.

The data on this page has been compiled from LifeSpan internal sources, the National Center for Biotechnology Information (NCBI), and The Universal Protein Resource (UniProt).

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