Alternative titles; symbols
HGNC Approved Gene Symbol: RRM2
Cytogenetic location: 2p25.1 Genomic coordinates (GRCh38): 2:10,122,568-10,211,010 (from NCBI)
The RRM2 gene encodes the small subunit (R2) of ribonucleotide reductase, the heterodimeric enzyme that catalyzes the rate-limiting step for the production of deoxyribonucleotides needed for DNA synthesis (summary by Pavloff et al., 1992).
Pavloff et al. (1992) cloned human RRM1 (180410) and RRM2 cDNAs from a breast carcinoma cDNA library. The deduced 389-amino acid RRM2 protein has a molecular mass of 45 kD and is 1 amino acid shorter than the equivalent mouse protein. The human and mouse RRM2 proteins share 96% homology in the C terminus, but only 69% in the first 68 residues in the N terminus.
In dividing cells, ribonucleotide reductase is essential for the production of deoxyribonucleotides before DNA synthesis in S phase. Neither of its 2 subunits, R1 or R2, are detectable in quiescent cells. In cycling cells, RRM2 mRNA and protein are present throughout the cell cycle (summary by Parker et al., 1994).
Using a library of endoribonuclease-prepared short interfering RNAs (esiRNAs), Kittler et al. (2004) identified 37 genes required for cell division, one of which was RRM2. These 37 genes included several splicing factors for which knockdown generates mitotic spindle defects. In addition, a putative nuclear-export terminator was found to speed up cell proliferation and mitotic progression after knockdown.
Yang-Feng et al. (1986, 1987) carried out chromosomal mapping of RRM2 by means of a full-length mouse cDNA. By Southern blot analysis of interspecies somatic cell hybrid lines and by in situ hybridization, Yang-Feng et al. (1987) found that the 4 chromosomal sites carrying M2-related sequences are 1p33-p31, 1q21-q23, 2p25-p24, and Xp21-p11. In the mouse, M2 sequences were found on chromosomes 4, 7, 12, and 13 by somatic cell hybrid studies. By Southern analysis of human and mouse hydroxyurea-resistant cells that overproduce M2 due to gene amplification, Yang-Feng et al. (1987) identified the amplified restriction fragments as those that map to human chromosome 2 and to mouse chromosome 12. The sites other than 2p probably represent pseudogenes, particularly the ones on the X chromosome since active genes on mammalian X chromosomes are conserved and no RRM2 sequence was found on the mouse X chromosome. Ornithine decarboxylase (ODC; 165640) is coamplified with RRM2 in human and rodent hydroxyurea-resistant cell lines. Using cDNA clones, Yang-Feng et al. (1987) mapped ODC to the same region of human chromosome 2. In an RRM2 overproducing mouse cell line, they found amplification of the chromosome 12-specific restriction fragments. Thus, the functional loci of both RRM2 and ODC are on murine chromosome 12.
Kittler, R., Putz, G., Pelletier, L., Poser, I., Heninger, A.-K., Drechsel, D., Fischer, S., Konstantinova, I., Habermann, B., Grabner, H., Yaspo, M.-L., Himmelbauer, H., Korn, B., Neugebauer, K., Pisabarro, M. T., Buchholz, F. An endoribonuclease-prepared siRNA screen in human cells identifies genes essential for cell division. Nature 432: 1036-1040, 2004. [PubMed: 15616564] [Full Text: https://doi.org/10.1038/nature03159]
Parker, N. J., Begley, C. G., Fox, R. M. Human R1 subunit of ribonucleotide reductase (RRM1): 5-prime flanking region of the gene. Genomics 19: 91-96, 1994. [PubMed: 8188248] [Full Text: https://doi.org/10.1006/geno.1994.1017]
Pavloff, N., Rivard, D., Masson, S., Shen, S.-H., Mes-Masson, A.-M. Sequence analysis of the large and small subunits of human ribonucleotide reductase. DNA Seq. 2: 227-234, 1992. [PubMed: 1627826] [Full Text: https://doi.org/10.3109/10425179209020807]
Yang-Feng, T. L., Barton, D. E., Thelander, L., Lewis, W. H., Srinivasan, P. R., Francke, U. Ribonucleotide reductase M2 subunit sequences mapped to four different chromosomal sites in humans and mice: functional locus identified by its amplification in hydroxyurea-resistant cell lines. Genomics 1: 77-86, 1987. [PubMed: 3311968] [Full Text: https://doi.org/10.1016/0888-7543(87)90108-x]
Yang-Feng, T. L., Thelander, L., Lewis, W. H., Srinivasan, P. R., Francke, U. Gene localization of the ribonucleotide reductase M2 subunit and of related and co-amplified sequences on human and mouse chromosomes. (Abstract) Am. J. Hum. Genet. 39: A174 only, 1986.