Characterization of the human ribonucleotide reductase M2 subunit gene; genomic structure and promoter analyses

Ribonucleotide Reductase (RR) is a rate-limiting enzyme in DNA synthesis and repair consisting of two subunits, M1 and M2. RRM2 plays a role in cell proliferation, tumorgenicity, metastasis and drug resistance. To better understand the regulation of RRM2, we have sequenced the entire human RRM2 gene. Approximately 10.3 kb of genomic DNA was sequenced and deposited to GenBank (accession number AY032750). Intron/exon junctions were identified and the gene was found to consist of ten exons. Two transcription initiation sites were identified and correspond to mRNA transcripts of 3.4 kb and 1.65 kb. Deletion analysis of the 5′-flanking region showed that there was promoter activity consistent with the presence of two separate promoters driving expression of the two RRM2 transcripts. A thorough analysis of the genomic sequence and promoter regions of the RRM2 gene will provide insight into the processes involved in tumor transformation and drug resistance.