RRM2 explained

Ribonucleoside-diphosphate reductase subunit M2, also known as ribonucleotide reductase small subunit, is an enzyme that in humans is encoded by the RRM2 gene.^{[1] [2]}

Function

This gene encodes one of two non-identical subunits for ribonucleotide reductase. This reductase catalyzes the formation of deoxyribonucleotides from ribonucleotides. Synthesis of the encoded protein (M2) is regulated in a cell-cycle dependent fashion. Transcription from this gene can initiate from alternative promoters, which results in two isoforms that differ in the lengths of their N-termini.^[1]

Further reading

• Lin ZP, Belcourt MF, Cory JG, Sartorelli AC . Stable suppression of the R2 subunit of ribonucleotide reductase by R2-targeted short interference RNA sensitizes p53(-/-) HCT-116 colon cancer cells to DNA-damaging agents and ribonucleotide reductase inhibitors. . J. Biol. Chem. . 279 . 26 . 27030–8 . 2004 . 15096505 . 10.1074/jbc.M402056200 . free .
• Zhang K, Hu S, Wu J, etal . Overexpression of RRM2 decreases thrombspondin-1 and increases VEGF production in human cancer cells in vitro and in vivo: implication of RRM2 in angiogenesis . Mol. Cancer . 8 . 11 . 2009 . 19250552 . 2662784 . 10.1186/1476-4598-8-11 . free .
• Cohen D, Adamovich Y, Reuven N, Shaul Y . Hepatitis B virus activates deoxynucleotide synthesis in nondividing hepatocytes by targeting the R2 gene . Hepatology . 51 . 5 . 1538–46 . 2010 . 20155784 . 10.1002/hep.23519 . 30044162 . free .
• Ferrandina G, Mey V, Nannizzi S, etal . Expression of nucleoside transporters, deoxycitidine kinase, ribonucleotide reductase regulatory subunits, and gemcitabine catabolic enzymes in primary ovarian cancer . Cancer Chemother. Pharmacol. . 65 . 4 . 679–86 . 2010 . 19639316 . 10.1007/s00280-009-1073-y . 13276061 .
• Qiu W, Zhou B, Darwish D, etal . Characterization of enzymatic properties of human ribonucleotide reductase holoenzyme reconstituted in vitro from hRRM1, hRRM2, and p53R2 subunits . Biochem. Biophys. Res. Commun. . 340 . 2 . 428–34 . 2006 . 16376858 . 10.1016/j.bbrc.2005.12.019 .
• Boukovinas I, Papadaki C, Mendez P, etal . Tumor BRCA1, RRM1 and RRM2 mRNA Expression Levels and Clinical Response to First-Line Gemcitabine plus Docetaxel in Non-Small-Cell Lung Cancer Patients . PLOS ONE . 3 . 11 . e3695 . 2008 . 19002265 . 2579656 . 10.1371/journal.pone.0003695 . 2008PLoSO...3.3695B . Ramqvist . Torbjorn . free .
• Beausoleil SA, Villén J, Gerber SA. A probability-based approach for high-throughput protein phosphorylation analysis and site localization . Nat. Biotechnol. . 24 . 10 . 1285–92 . 2006 . 16964243 . 10.1038/nbt1240 . 14294292 . etal.
• Kimura K, Wakamatsu A, Suzuki Y, etal . Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes . Genome Res. . 16 . 1 . 55–65 . 2006 . 16344560 . 1356129 . 10.1101/gr.4039406 .
• Duxbury MS, Whang EE . RRM2 induces NF-kappaB-dependent MMP-9 activation and enhances cellular invasiveness . Biochem. Biophys. Res. Commun. . 354 . 1 . 190–6 . 2007 . 17222798 . 10.1016/j.bbrc.2006.12.177 .
• Attia S, Kolesar J, Mahoney MR, etal . A phase 2 consortium (P2C) trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) for advanced adenocarcinoma of the pancreas . Invest New Drugs . 26 . 4 . 369–79 . 2008 . 18278438 . 10.1007/s10637-008-9123-6 . 4461052 .
• Couch FJ, Wang X, Bamlet WR, etal . Association of Mitotic Regulation Pathway Polymorphisms with Pancreatic Cancer Risk and Outcome . Cancer Epidemiol. Biomarkers Prev. . 19 . 1 . 251–7 . 2010 . 20056645 . 2805468 . 10.1158/1055-9965.EPI-09-0629 .
• Réjiba S, Bigand C, Parmentier C, Hajri A . Gemcitabine-Based Chemogene Therapy for Pancreatic Cancer Using Ad-dCK::UMK GDEPT and TS/RR siRNA Strategies . Neoplasia . 11 . 7 . 637–50 . 2009 . 19568409 . 2697350 . 10.1593/neo.81686.
• Kolesar J, Huang W, Eickhoff J, etal . Evaluation of mRNA by Q-RTPCR and Protein Expression by AQUA of the M2 Subunit of Ribonucleotide Reductase (RRM2) in Human Tumors . Cancer Chemother. Pharmacol. . 64 . 1 . 79–86 . 2009 . 18941749 . 10.1007/s00280-008-0845-0 . 3043989 .
• Hillier LW, Graves TA, Fulton RS, etal . Generation and annotation of the DNA sequences of human chromosomes 2 and 4 . Nature . 434 . 7034 . 724–31 . 2005 . 15815621 . 10.1038/nature03466 . 2005Natur.434..724H . free .
• Book: Liu X, Xue L, Yen Y . Advanced Protocols in Oxidative Stress I . Redox Property of Ribonucleotide Reductase Small Subunit M2 and p53R2 . 477 . 195–206 . 2008 . 19082948 . 10.1007/978-1-60327-517-0_15 . Methods In Molecular Biology . 978-1-60327-218-6 . registration . https://archive.org/details/advancedprotocol00dona/page/195 .
• 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 . 528928 . 10.1101/gr.2596504 .
• Bourdon A, Minai L, Serre V, etal . Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion . Nat. Genet. . 39 . 6 . 776–80 . 2007 . 17486094 . 10.1038/ng2040 . 22103978 .
• Souglakos J, Boukovinas I, Taron M, etal . Ribonucleotide reductase subunits M1 and M2 mRNA expression levels and clinical outcome of lung adenocarcinoma patients treated with docetaxel/gemcitabine . Br. J. Cancer . 98 . 10 . 1710–5 . 2008 . 18414411 . 2391126 . 10.1038/sj.bjc.6604344 .
• Zhang YW, Jones TL, Martin SE, etal . Implication of Checkpoint Kinase-dependent Up-regulation of Ribonucleotide Reductase R2 in DNA Damage Response . J. Biol. Chem. . 284 . 27 . 18085–95 . 2009 . 19416980 . 2709352 . 10.1074/jbc.M109.003020 . free .

Notes and References

1. Web site: Entrez Gene: ribonucleotide reductase M2.
2. Pavloff N, Rivard D, Masson S, Shen SH, Mes-Masson AM . Sequence analysis of the large and small subunits of human ribonucleotide reductase . DNA Seq. . 2 . 4 . 227–34 . 1992 . 1627826 . 10.3109/10425179209020807.