Ribonucleoside-Diphosphate Reductase, Large Subunit (RRM1) Antibody – Rabbit Polyclonal

This gene encodes one of two non-identical subunits that constitute ribonucleoside-diphosphate reductase, an enzyme essential for the production of deoxyribonucleotides prior to DNA synthesis in S phase of dividing cells. It is one of several genes located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocrotical carcinoma, and lung, ovarian, and breast cancer. This gene may play a role in malignancies and disease that involve this region. [provided by RefSeq, Jul 2008]

Function: Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.

Catalytic activity: 2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O = ribonucleoside diphosphate + thioredoxin. Ref.8

Enzyme regulation: Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding to separate specificity and activation sites on the M1 subunit. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction and dTTP favors GDP reduction. Stimulated by ATP and inhibited by dATP binding to the activity site. Ref.6 Ref.8

Pathway: Genetic information processing; DNA replication.

Subunit structure: Heterodimer of a large and a small subunit. Heterodimer with small subunit RRM2 or RRM2B. The heterodimer with RRM2 has higher catalytic activity than the heterodimer with RRM2B. Ref.8

Subcellular location: Cytoplasm.

Miscellaneous: Two distinct regulatory sites have been defined: the specificity site, which controls substrate specificity, and the activity site which regulates overall catalytic activity. A substrate-binding catalytic site, located on M1, is formed only in the presence of the second subunit M2.The level of the enzyme activity is closely correlated with the growth rate of a cell and appears to vary with the cell cycle.

Sequence similarities: Belongs to the ribonucleoside diphosphate reductase large chain family.Contains 1 ATP-cone domain.