The protein encoded by this gene is one of two human homologs of Saccharomyces cerevisiae Rad23, a protein involved in nucleotide excision repair (NER). This protein was found to be a component of the protein complex that specifically complements the NER defect of xeroderma pigmentosum group C (XP-c) cell extracts in vitro. This protein was also shown to interact with, and elevate the nucleotide excision activity of 3-methyladenine-DNA glycosylase (MPG), which suggested a role in DNA damage recognition in base excision repair. This protein contains an N-terminal ubiquitin-like domain, which was reported to interact with 26S proteasome, and thus this protein may be involved in the ubiquitin mediated proteolytic pathway in cells.[3]
Role in DNA repair
The complex of XPC-RAD23B is the initial damage recognition factor in global genomic nucleotide excision repair (GG-NER). XPC-RAD23B recognizes a wide variety of lesions that thermodynamically destabilize DNA duplexes, including UV-induced photoproducts (cyclopyrimidine dimers and 6-4 photoproducts ), adducts formed by environmental mutagens such as benzo[a]pyrene or various aromatic amines, certain oxidative endogenous lesions such as cyclopurines and adducts formed by cancer chemotherapeutic drugs such as cisplatin. The presence of XPC-RAD23B is required for assembly of the other core NER factors and progression through the NER pathway both in vitro and in vivo.[4] Although most studies have been performed with XPC-RAD23B, it is part of a trimeric complex with centrin-2, a calcium-binding protein of the calmodulin family.[4]
A deficiency in expression of a DNA repair gene increases the risk for cancer (see Deficient DNA repair in carcinogenesis). The expression of RAD23B is reduced in tumor tissue of women with breast cancer.[9] A low percentage of RAD23B positive nuclei in high grade breast cancer was also observed.[10]
RAD23B was substantially reduced by promoter methylation in a cell line derived from multiple myeloma.[5] and reduced by promoter methylation in a small proportion of non-small cell lung cancer (NSCLC) tumours.[6]
RAD23B appears to be one of 26 DNA repair genes that are epigenetically repressed in various cancers (see Cancer epigenetics).
↑van der Spek PJ, Smit EM, Beverloo HB, Sugasawa K, Masutani C, Hanaoka F, Hoeijmakers JH, Hagemeijer A (Oct 1994). "Chromosomal localization of three repair genes: the xeroderma pigmentosum group C gene and two human homologs of yeast RAD23". Genomics. 23 (3): 651–8. doi:10.1006/geno.1994.1554. PMID7851894.
↑Linge A, Maurya P, Friedrich K, Baretton GB, Kelly S, Henry M, Clynes M, Larkin A, Meleady P (Jul 2014). "Identification and functional validation of RAD23B as a potential protein in human breast cancer progression". Journal of Proteome Research. 13 (7): 3212–22. doi:10.1021/pr4012156. PMID24897598.
↑Hiyama H, Yokoi M, Masutani C, Sugasawa K, Maekawa T, Tanaka K, Hoeijmakers JH, Hanaoka F (Sep 1999). "Interaction of hHR23 with S5a. The ubiquitin-like domain of hHR23 mediates interaction with S5a subunit of 26 S proteasome". The Journal of Biological Chemistry. 274 (39): 28019–25. doi:10.1074/jbc.274.39.28019. PMID10488153.
↑Wang G, Sawai N, Kotliarova S, Kanazawa I, Nukina N (Jul 2000). "Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B". Human Molecular Genetics. 9 (12): 1795–803. doi:10.1093/hmg/9.12.1795. PMID10915768.
Further reading
Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Sugasawa K, Ng JM, Masutani C, Iwai S, van der Spek PJ, Eker AP, Hanaoka F, Bootsma D, Hoeijmakers JH (Aug 1998). "Xeroderma pigmentosum group C protein complex is the initiator of global genome nucleotide excision repair". Molecular Cell. 2 (2): 223–32. doi:10.1016/S1097-2765(00)80132-X. PMID9734359.
Hiyama H, Yokoi M, Masutani C, Sugasawa K, Maekawa T, Tanaka K, Hoeijmakers JH, Hanaoka F (Sep 1999). "Interaction of hHR23 with S5a. The ubiquitin-like domain of hHR23 mediates interaction with S5a subunit of 26 S proteasome". The Journal of Biological Chemistry. 274 (39): 28019–25. doi:10.1074/jbc.274.39.28019. PMID10488153.
Miao F, Bouziane M, Dammann R, Masutani C, Hanaoka F, Pfeifer G, O'Connor TR (Sep 2000). "3-Methyladenine-DNA glycosylase (MPG protein) interacts with human RAD23 proteins". The Journal of Biological Chemistry. 275 (37): 28433–8. doi:10.1074/jbc.M001064200. PMID10854423.
Wang G, Sawai N, Kotliarova S, Kanazawa I, Nukina N (Jul 2000). "Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B". Human Molecular Genetics. 9 (12): 1795–803. doi:10.1093/hmg/9.12.1795. PMID10915768.
Araki M, Masutani C, Takemura M, Uchida A, Sugasawa K, Kondoh J, Ohkuma Y, Hanaoka F (Jun 2001). "Centrosome protein centrin 2/caltractin 1 is part of the xeroderma pigmentosum group C complex that initiates global genome nucleotide excision repair". The Journal of Biological Chemistry. 276 (22): 18665–72. doi:10.1074/jbc.M100855200. PMID11279143.
Walters KJ, Kleijnen MF, Goh AM, Wagner G, Howley PM (Feb 2002). "Structural studies of the interaction between ubiquitin family proteins and proteasome subunit S5a". Biochemistry. 41 (6): 1767–77. doi:10.1021/bi011892y. PMID11827521.
Lee SM, Li ML, Tse YC, Leung SC, Lee MM, Tsui SK, Fung KP, Lee CY, Waye MM (Sep 2002). "Paeoniae Radix, a Chinese herbal extract, inhibit hepatoma cells growth by inducing apoptosis in a p53 independent pathway". Life Sciences. 71 (19): 2267–77. doi:10.1016/S0024-3205(02)01962-8. PMID12215374.
Ryu KS, Lee KJ, Bae SH, Kim BK, Kim KA, Choi BS (Sep 2003). "Binding surface mapping of intra- and interdomain interactions among hHR23B, ubiquitin, and polyubiquitin binding site 2 of S5a". The Journal of Biological Chemistry. 278 (38): 36621–7. doi:10.1074/jbc.M304628200. PMID12832454.
Fujiwara K, Tenno T, Sugasawa K, Jee JG, Ohki I, Kojima C, Tochio H, Hiroaki H, Hanaoka F, Shirakawa M (Feb 2004). "Structure of the ubiquitin-interacting motif of S5a bound to the ubiquitin-like domain of HR23B". The Journal of Biological Chemistry. 279 (6): 4760–7. doi:10.1074/jbc.M309448200. PMID14585839.
