Work

Pools and Pols: Mechanism of a mutator phenotype

Year: 2015

Type: article

Abstract: The maintenance of the human genome is dependent upon several cellular processes including DNA replication. Ordinarily, DNA replication is an exceptionally faithful process, with approximately one error occurring for every 109–1010 nucleotides (1, 2). High-fidelity replicative DNA polymerases with exonucleolytic proofreading activity, along with DNA mismatch repair machinery, are responsible for accurate DNA synthesis. DNA polymerase δ (pol δ) and polymerase e (pol e) are two essential replicative lagging and leading strand polymerases, respectively, that ensure efficient and high-fidelity genome replication (3–5). Replicative polymerase variants have recently been identified in human tumors that harbor enormous numbers of mutations. In recent studies reported in PNAS, Mertz et al. and Williams et al. provide evidence that this hypermutator phenotype results from expansion of deoxyribonucleoside triphosphate (dNTP) pools (6, 7).

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1505169112

Authors: Christal D. Sohl, Sreerupa Ray, Joann B. Sweasy

Institution: Yale University

Language: English

Topic: Evolution and Genetic Dynamics

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funder: National Cancer Institute

Awards: DNA Polymerase Beta and Mutagenesis, G5261373027