title: Cellular roles of DNA polymerase beta.
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.
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Sreerupa
authors.initials: S
authors.lastname: Ray
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Miriam Rose
authors.initials: MR
authors.lastname: Menezes
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Alireza
authors.initials: A
authors.lastname: Senejani
authors.affiliation: Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Joann B
authors.initials: JB
authors.lastname: Sweasy
mesh_terms: D000818:Animals; D019951:DNA Polymerase beta / Q000235:genetics* / Q000378:metabolism*; D004260:DNA Repair / Q000235:genetics*; D042822:Genomic Instability; D018095:Germ-Line Mutation; D006801:Humans; D008540:Meiosis / Q000235:genetics; D051379:Mice; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism
chemical_list: D019951:DNA Polymerase beta
keywords: DNA polymerase beta; fidelity of DNA synthesis; meiosis