RRM2B
RRM2B (Ribonucleotide reductase regulatory TP53 inducible subunit M2B) is a gene that encodes a protein involved in the synthesis of deoxyribonucleotides from ribonucleotides, which is a crucial step in DNA replication and repair. This protein is a part of the ribonucleotide reductase complex, which is essential for DNA synthesis and repair, particularly under conditions of cellular stress.
Structure
The RRM2B protein is a small subunit of the ribonucleotide reductase complex. It is known to form a heterodimer with the large subunit, RRM1, to become active. The RRM2B subunit is inducible by the tumor suppressor protein TP53, which plays a critical role in the cellular response to DNA damage.
Function
RRM2B is primarily involved in the maintenance of the deoxyribonucleotide pool during DNA repair and replication. It is particularly important in the mitochondrial DNA synthesis and repair processes. The protein is upregulated in response to DNA damage and is thought to help maintain genomic stability by providing the necessary deoxyribonucleotides for DNA repair.
Clinical Significance
Mutations in the RRM2B gene have been associated with several disorders, including mitochondrial DNA depletion syndromes. These are a group of disorders characterized by a significant reduction in mitochondrial DNA copy number, leading to a variety of clinical manifestations such as muscle weakness, neurological deficits, and organ failure.
RRM2B has also been implicated in cancer biology. Its expression is regulated by TP53, a key tumor suppressor, and alterations in RRM2B expression can affect tumor growth and response to therapy. Overexpression of RRM2B has been observed in certain cancers and is thought to contribute to chemoresistance.
Research Directions
Current research on RRM2B focuses on understanding its role in mitochondrial function and its potential as a therapeutic target in cancer. Studies are also exploring the mechanisms by which RRM2B is regulated by TP53 and other cellular stress signals.
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Contributors: Prab R. Tumpati, MD