Ribonucleotide-diphosphate reductase subunit M2 B is an
enzyme that in humans is encoded by the RRM2Bgene.[5][6][7][8] The gene encoding the RRM2B protein is located on
chromosome 8, at position 8q23.1. The gene and its products are also known by designations MTDPS8A, MTDPS8B, and p53R2.
Function
RRM2B codes for one of two versions of the R2 subunit of
ribonucleotide reductase, which generates nucleotide precursors required for DNA replication by reducing
ribonucleosidediphosphates to deoxyribonucloside diphosphates. The version of R2 encoded by RRM2B is induced by
p53, and is required for normal DNA repair and
mtDNA synthesis in non-proliferating cells. The other form of R2 is expressed only in dividing cells.[9]
Mutations in this gene have been shown to cause progressive external
ophthalmoplegia.[16]
Increased expression of RRM2B has been correlated with
gemcitabine resistance in human cholangiocarcinoma cells[17] and may be predictive of lack of clinical benefit from gemcitabine for human cancers.
^Acham-Roschitz B, Plecko B, Lindbichler F, Bittner R, Mache CJ, Sperl W, Mayr JA (November 2009). "A novel mutation of the RRM2B gene in an infant with early fatal encephalomyopathy, central hypomyelination, and tubulopathy". Molecular Genetics and Metabolism. 98 (3): 300–4.
doi:
10.1016/j.ymgme.2009.06.012.
PMID19616983.
^Kropach N, Shkalim-Zemer V, Orenstein N, Scheuerman O, Straussberg R (May 2017). "Novel RRM2B Mutation and Severe Mitochondrial DNA Depletion: Report of 2 Cases and Review of the Literature". Neuropediatrics. 48 (6): 456–462.
doi:
10.1055/s-0037-1601867.
PMID28482374.
S2CID7809119.
^Sato J, Kimura T, Saito T, Anazawa T, Kenjo A, Sato Y, Tsuchiya T, Gotoh M (September 2011). "Gene expression analysis for predicting gemcitabine resistance in human cholangiocarcinoma". Journal of Hepato-Biliary-Pancreatic Sciences. 18 (5): 700–11.
doi:
10.1007/s00534-011-0376-7.
PMID21451941.
S2CID19975519.
Yamaguchi T, Matsuda K, Sagiya Y, Iwadate M, Fujino MA, Nakamura Y, Arakawa H (November 2001). "p53R2-dependent pathway for DNA synthesis in a p53-regulated cell cycle checkpoint". Cancer Research. 61 (22): 8256–62.
PMID11719458.
Yanamoto S, Kawasaki G, Yoshitomi I, Mizuno A (February 2003). "Expression of p53R2, newly p53 target in oral normal epithelium, epithelial dysplasia and squamous cell carcinoma". Cancer Letters. 190 (2): 233–43.
doi:
10.1016/S0304-3835(02)00588-8.
PMID12565178.
Xue L, Zhou B, Liu X, Qiu W, Jin Z, Yen Y (March 2003). "Wild-type p53 regulates human ribonucleotide reductase by protein-protein interaction with p53R2 as well as hRRM2 subunits". Cancer Research. 63 (5): 980–6.
PMID12615712.
Zhou B, Liu X, Mo X, Xue L, Darwish D, Qiu W, Shih J, Hwu EB, Luh F, Yen Y (October 2003). "The human ribonucleotide reductase subunit hRRM2 complements p53R2 in response to UV-induced DNA repair in cells with mutant p53". Cancer Research. 63 (20): 6583–94.
PMID14583450.
Ohno K, Tanaka-Azuma Y, Yoneda Y, Yamada T (December 2005). "Genotoxicity test system based on p53R2 gene expression in human cells: examination with 80 chemicals". Mutation Research. 588 (1): 47–57.
doi:
10.1016/j.mrgentox.2005.09.002.
PMID16236544.
Qiu W, Zhou B, Darwish D, Shao J, Yen Y (February 2006). "Characterization of enzymatic properties of human ribonucleotide reductase holoenzyme reconstituted in vitro from hRRM1, hRRM2, and p53R2 subunits". Biochemical and Biophysical Research Communications. 340 (2): 428–34.
doi:
10.1016/j.bbrc.2005.12.019.
PMID16376858.
Okumura H, Natsugoe S, Yokomakura N, Kita Y, Matsumoto M, Uchikado Y, Setoyama T, Owaki T, Ishigami S, Aikou T (June 2006). "Expression of p53R2 is related to prognosis in patients with esophageal squamous cell carcinoma". Clinical Cancer Research. 12 (12): 3740–5.
doi:
10.1158/1078-0432.CCR-05-2416.
PMID16778101.
S2CID15106205.
Yen Y, Chu B, Yen C, Shih J, Zhou B (2007). "Enzymatic property analysis of p53R2 subunit of human ribonucleotide reductase". Advances in Enzyme Regulation. 46: 235–47.
doi:
10.1016/j.advenzreg.2006.01.016.
PMID16846634.
Lembo D, Donalisio M, Cornaglia M, Azzimonti B, Demurtas A, Landolfo S (December 2006). "Effect of high-risk human papillomavirus oncoproteins on p53R2 gene expression after DNA damage". Virus Research. 122 (1–2): 189–93.
doi:
10.1016/j.virusres.2006.06.011.
PMID16872707.