Premium
DNA polymerase ε and its roles in genome stability
Author(s) -
Henninger Erin E.,
Pursell Zachary F.
Publication year - 2014
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.1276
Subject(s) - dna polymerase , proofreading , dna polymerase ii , biology , exonuclease , genetics , dna replication , genome instability , polymerase , microsatellite instability , dna mismatch repair , genome , microbiology and biotechnology , gene , dna , dna repair , dna damage , microsatellite , polymerase chain reaction , reverse transcriptase , allele
DNA Polymerase Epsilon (Pol ε) is one of three DNA Polymerases (along with Pol δ and Pol α) required for nuclear DNA replication in eukaryotes. Pol ε is comprised of four subunits, the largest of which is encoded by the POLE gene and contains the catalytic polymerase and exonuclease activities. The 3′‐5′ exonuclease proofreading activity is able to correct DNA synthesis errors and helps protect against genome instability. Recent cancer genome sequencing efforts have shown that 3% of colorectal and 7% of endometrial cancers contain mutations within the exonuclease domain of POLE and are associated with significantly elevated levels of single nucleotide substitutions (15‐500 per Mb) and microsatellite stability. POLE mutations have also been found in other tumor types, though at lower frequency, suggesting roles in tumorigenesis more broadly in different tissue types. In addition to its proofreading activity, Pol ε contributes to genome stability through multiple mechanisms that are discussed in this review. © 2014 IUBMB Life, 66(5):339–351, 2014