Cellular roles of DNA polymerase beta

Yale J Biol Med. 2013 Dec 13;86(4):463-9.

Abstract

Since its discovery and purification in 1971, DNA polymerase ß (Pol ß) is one of the most well-studied DNA polymerases. Pol ß is a key enzyme in the base excision repair (BER) pathway that functions in gap filling DNA synthesis subsequent to the excision of damaged DNA bases. A major focus of our studies is on the cellular roles of Pol ß. We have shown that germline and tumor-associated variants of Pol ß catalyze aberrant BER that leads to genomic instability and cellular transformation. Our studies suggest that Pol ß is critical for the maintenance of genomic stability and that it is a tumor suppressor. We have also shown that Pol ß functions during Prophase I of meiosis. Pol ß localizes to the synaptonemal complex and is critical for removal of the Spo11 complex from the 5' ends of double-strand breaks. Studies with Pol ß mutant mice are currently being undertaken to more clearly understand the function of Pol ß during meiosis. In this review, we will highlight our contributions from our studies of Pol ß germline and cancer-associated variants.

Keywords: DNA polymerase beta; fidelity of DNA synthesis; meiosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • DNA Polymerase beta / genetics*
  • DNA Polymerase beta / metabolism*
  • DNA Repair / genetics*
  • Genomic Instability*
  • Germ-Line Mutation*
  • Humans
  • Meiosis / genetics
  • Mice
  • Models, Genetic
  • Neoplasms / genetics
  • Neoplasms / metabolism

Substances

  • DNA Polymerase beta