RAD23B

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RAD23B
Protein RAD23B PDB 1dv0.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases RAD23B, HHR23B, HR23B, P58, RAD23 homolog B, nucleotide excision repair protein
External IDs MGI: 105128 HomoloGene: 37704 GeneCards: RAD23B
RNA expression pattern
PBB GE RAD23B 201222 s at fs.png

PBB GE RAD23B 201223 s at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002874
NM_001244713
NM_001244724

NM_009011

RefSeq (protein)

NP_001231642
NP_001231653
NP_002865

NP_033037.2
NP_033037

Location (UCSC) Chr 9: 107.28 – 107.33 Mb Chr 4: 55.35 – 55.39 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

UV excision repair protein RAD23 homolog B is a protein that in humans is encoded by the RAD23B gene.[3][4]

Function[edit]

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.[5]

Role in DNA repair[edit]

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.[6] 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.[6]

Epigenetic repression of RAD23[edit]

The protein expression level of RAD23B can be epigenetically repressed, either by promoter methylation of the RAD23B gene[7][8] or by either of two microRNAs (miR-744-3p[9] or miR-373[10]).

Deficiency of RAD23B in cancer[edit]

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.[11] A low percentage of RAD23B positive nuclei in high grade breast cancer was also observed.[12]

RAD23B was substantially reduced by promoter methylation in a cell line derived from multiple myeloma.[7] and reduced by promoter methylation in a small proportion of non-small cell lung cancer (NSCLC) tumours.[8]

RAD23B appears to be one of 26 DNA repair genes that are epigenetically repressed in various cancers (see Cancer epigenetics).

Interactions[edit]

RAD23B has been shown to interact with PSMD4[13] and Ataxin 3.[14]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ 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. PMID 7851894. 
  4. ^ Masutani C, Sugasawa K, Yanagisawa J, Sonoyama T, Ui M, Enomoto T, Takio K, Tanaka K, van der Spek PJ, Bootsma D (Apr 1994). "Purification and cloning of a nucleotide excision repair complex involving the xeroderma pigmentosum group C protein and a human homologue of yeast RAD23". The EMBO Journal. 13 (8): 1831–43. PMC 395023Freely accessible. PMID 8168482. 
  5. ^ "Entrez Gene: RAD23B RAD23 homolog B (S. cerevisiae)". 
  6. ^ a b Schärer OD (Oct 2013). "Nucleotide excision repair in eukaryotes". Cold Spring Harbor Perspectives in Biology. 5 (10): a012609. doi:10.1101/cshperspect.a012609. PMC 3783044Freely accessible. PMID 24086042. 
  7. ^ a b Peng B, Hodge DR, Thomas SB, Cherry JM, Munroe DJ, Pompeia C, Xiao W, Farrar WL (Feb 2005). "Epigenetic silencing of the human nucleotide excision repair gene, hHR23B, in interleukin-6-responsive multiple myeloma KAS-6/1 cells". The Journal of Biological Chemistry. 280 (6): 4182–7. doi:10.1074/jbc.M412566200. PMID 15550378. 
  8. ^ a b Do H, Wong NC, Murone C, John T, Solomon B, Mitchell PL, Dobrovic A (2014). "A critical re-assessment of DNA repair gene promoter methylation in non-small cell lung carcinoma". Scientific Reports. 4: 4186. doi:10.1038/srep04186. PMC 3935198Freely accessible. PMID 24569633. 
  9. ^ Hatano K, Kumar B, Zhang Y, Coulter JB, Hedayati M, Mears B, Ni X, Kudrolli TA, Chowdhury WH, Rodriguez R, DeWeese TL, Lupold SE (Apr 2015). "A functional screen identifies miRNAs that inhibit DNA repair and sensitize prostate cancer cells to ionizing radiation". Nucleic Acids Research. 43 (8): 4075–86. doi:10.1093/nar/gkv273. PMC 4417178Freely accessible. PMID 25845598. 
  10. ^ Crosby ME, Kulshreshtha R, Ivan M, Glazer PM (Feb 2009). "MicroRNA regulation of DNA repair gene expression in hypoxic stress". Cancer Research. 69 (3): 1221–9. doi:10.1158/0008-5472.CAN-08-2516. PMC 2997438Freely accessible. PMID 19141645. 
  11. ^ Matta J, Morales L, Dutil J, Bayona M, Alvarez C, Suarez E (Feb 2013). "Differential expression of DNA repair genes in Hispanic women with breast cancer". Molecular Cancer Biology. 1 (1): 54. doi:10.9777/mcb.2013.10006. PMC 4189824Freely accessible. PMID 25309843. 
  12. ^ 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. PMID 24897598. 
  13. ^ 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. PMID 10488153. 
  14. ^ 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. PMID 10915768. 

Further reading[edit]