RAD54B
DNA repair and recombination protein RAD54B is a protein that in humans is encoded by the RAD54B gene.[5][6][7]
| RAD54B | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | RAD54B, RDH54, RAD54 homolog B (S. cerevisiae), RAD54 homolog B | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 604289 MGI: 3605986 HomoloGene: 8240 GeneCards: RAD54B | ||||||||||||||||||||||||||||||||||||||||||||||||||
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The protein encoded by this gene belongs to the DEAD-like helicase superfamily. It shares similarity with Saccharomyces cerevisiae RAD54 and RDH54, both of which are involved in homologous recombination and repair of DNA. This protein binds to double-stranded DNA, and displays ATPase activity in the presence of DNA. This gene is highly expressed in testis and spleen, which suggests active roles in meiotic and mitotic recombination. Homozygous mutations of this gene were observed in primary lymphoma and colon cancer.[7]
Cancer
The RAD54B gene is somatically mutated or deleted in numerous types of cancer including colorectal cancer (~3.3%), breast cancer (~3.4%), and lung cancer (~2.6%).[8] In North America, these three cancers alone account for about 20,500 individuals diagnosed annually with RAD54B defective cancer. In a pre-clinical study, colon cancer cells defective in RAD54B were determined to be selectively killed by inhibitors of the DNA repair protein PARP1.[8] Inhibitors of PARP1 likely impede alternative DNA repair responses that might otherwise compensate for loss of the RAD54B pathway in cancer cells. Thus RAD54B-deficient cancer cells treated with a PARP1 inhibitor are apparently more vulnerable to killing by naturally occurring DNA damages than non-cancerous cells without a RAD54 defect (see article Synthetic lethality).
References
- GRCh38: Ensembl release 89: ENSG00000197275 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000078773 - Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- Hiramoto T, Nakanishi T, Sumiyoshi T, Fukuda T, Matsuura S, Tauchi H, Komatsu K, Shibasaki Y, Inui H, Watatani M, Yasutomi M, Sumii K, Kajiyama G, Kamada N, Miyagawa K, Kamiya K (Jun 1999). "Mutations of a novel human RAD54 homologue, RAD54B, in primary cancer". Oncogene. 18 (22): 3422–6. doi:10.1038/sj.onc.1202691. PMID 10362364.
- Tanaka K, Hiramoto T, Fukuda T, Miyagawa K (Sep 2000). "A novel human rad54 homologue, Rad54B, associates with Rad51". J Biol Chem. 275 (34): 26316–21. doi:10.1074/jbc.M910306199. PMID 10851248.
- "Entrez Gene: RAD54B RAD54 homolog B (S. cerevisiae)".
- McAndrew EN, Lepage CC, McManus KJ (December 2016). "The synthetic lethal killing of RAD54B-deficient colorectal cancer cells by PARP1 inhibition is enhanced with SOD1 inhibition". Oncotarget. 7 (52): 87417–87430. doi:10.18632/oncotarget.13654. PMC 5349998. PMID 27902462.
Further reading
- Miyagawa K, Tsuruga T, Kinomura A, et al. (2002). "A role for RAD54B in homologous recombination in human cells". EMBO J. 21 (1–2): 175–80. doi:10.1093/emboj/21.1.175. PMC 125815. PMID 11782437.
- Tanaka K, Kagawa W, Kinebuchi T, et al. (2002). "Human Rad54B is a double-stranded DNA-dependent ATPase and has biochemical properties different from its structural homolog in yeast, Tid1/Rdh54". Nucleic Acids Res. 30 (6): 1346–53. doi:10.1093/nar/30.6.1346. PMC 101365. PMID 11884632.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Sehorn MG, Sigurdsson S, Bussen W, et al. (2004). "Human meiotic recombinase Dmc1 promotes ATP-dependent homologous DNA strand exchange". Nature. 429 (6990): 433–7. doi:10.1038/nature02563. PMID 15164066. S2CID 4316803.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
- Wesoly J, Agarwal S, Sigurdsson S, et al. (2006). "Differential contributions of mammalian Rad54 paralogs to recombination, DNA damage repair, and meiosis". Mol. Cell. Biol. 26 (3): 976–89. doi:10.1128/MCB.26.3.976-989.2006. PMC 1347043. PMID 16428451.
- Sarai N, Kagawa W, Kinebuchi T, et al. (2006). "Stimulation of Dmc1-mediated DNA strand exchange by the human Rad54B protein". Nucleic Acids Res. 34 (16): 4429–37. doi:10.1093/nar/gkl562. PMC 1636354. PMID 16945962.
- Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
- Bryś M, Nowacka-Zawisza M, Romanowicz-Makowska H, et al. (2007). "Loss of heterozygosity in the RAD54B region is not predictive for breast carcinomas". Pol J Pathol. 58 (1): 3–6. PMID 17585536.