RAD54B explained

DNA repair and recombination protein RAD54B is a protein that in humans is encoded by the RAD54B gene.^{[1] [2] [3]}

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.^[4]

Interactions

RAD54B has been shown to interact with RAD51.

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%).^[5] 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. 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).

Further reading

• Miyagawa K, Tsuruga T, Kinomura A, etal . A role for RAD54B in homologous recombination in human cells. . EMBO J. . 21 . 1–2 . 175–80 . 2002 . 11782437 . 10.1093/emboj/21.1.175 . 125815 .
• Tanaka K, Kagawa W, Kinebuchi T, etal . 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 . 2002 . 11884632 . 10.1093/nar/30.6.1346 . 101365 .
• Strausberg RL, Feingold EA, Grouse LH, etal . 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 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Sehorn MG, Sigurdsson S, Bussen W, etal . Human meiotic recombinase Dmc1 promotes ATP-dependent homologous DNA strand exchange . Nature . 429 . 6990 . 433–7 . 2004 . 15164066 . 10.1038/nature02563 . 2004Natur.429..433S . 4316803 .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Rual JF, Venkatesan K, Hao T, etal . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Wesoly J, Agarwal S, Sigurdsson S, etal . Differential contributions of mammalian Rad54 paralogs to recombination, DNA damage repair, and meiosis . Mol. Cell. Biol. . 26 . 3 . 976–89 . 2006 . 16428451 . 10.1128/MCB.26.3.976-989.2006 . 1347043 .
• Sarai N, Kagawa W, Kinebuchi T, etal . Stimulation of Dmc1-mediated DNA strand exchange by the human Rad54B protein . Nucleic Acids Res. . 34 . 16 . 4429–37 . 2006 . 16945962 . 10.1093/nar/gkl562 . 1636354 .
• Ewing RM, Chu P, Elisma F, etal . Large-scale mapping of human protein-protein interactions by mass spectrometry . Mol. Syst. Biol. . 3 . 1. 89 . 2007 . 17353931 . 10.1038/msb4100134 . 1847948 .
• Bryś M, Nowacka-Zawisza M, Romanowicz-Makowska H, etal . Loss of heterozygosity in the RAD54B region is not predictive for breast carcinomas . Pol J Pathol . 58 . 1 . 3–6 . 2007 . 17585536 .

Notes and References

1. 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 . Mutations of a novel human RAD54 homologue, RAD54B, in primary cancer . Oncogene . 18 . 22 . 3422–6 . Jun 1999 . 10362364 . 10.1038/sj.onc.1202691 . 24095399 .
2. Tanaka K, Hiramoto T, Fukuda T, Miyagawa K . A novel human rad54 homologue, Rad54B, associates with Rad51 . J Biol Chem . 275 . 34 . 26316–21 . Sep 2000 . 10851248 . 10.1074/jbc.M910306199 . free .
3. Web site: Entrez Gene: RAD54B RAD54 homolog B (S. cerevisiae).
4. Web site: Entrez Gene: RAD54B RAD54 homolog B (S. cerevisiae).
5. McAndrew EN, Lepage CC, McManus KJ . The synthetic lethal killing of RAD54B-deficient colorectal cancer cells by PARP1 inhibition is enhanced with SOD1 inhibition . Oncotarget . 7 . 52 . 87417–87430 . December 2016 . 27902462 . 5349998 . 10.18632/oncotarget.13654 .