Replicative DNA polymerase defects in human cancers: Consequences, mechanisms, and implications for therapy.

ABSTRACT: The fidelity of DNA replication relies on three error avoidance mechanisms acting in series: nucleotide selectivity of replicative DNA polymerases, exonucleolytic proofreading, and post-replicative DNA mismatch repair (MMR). MMR defects are well known to be associated with increased cancer incidence. Due to advances in DNA sequencing technologies, the past several years have witnessed a long-predicted discovery of replicative DNA polymerase defects in sporadic and hereditary human cancers. The polymerase mutations preferentially affect conserved amino acid residues in the exonuclease domain and occur in tumors with an extremely high mutation load. Thus, a concept has formed that defective proofreading of replication errors triggers the development of these tumors. Recent studies of the mos

SUBMITTER: Barbari SR 

PROVIDER: S-EPMC5750057 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature