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.
Original language | English (US) |
---|---|
Pages (from-to) | 463-469 |
Number of pages | 7 |
Journal | Yale Journal of Biology and Medicine |
Volume | 86 |
Issue number | 4 |
State | Published - Dec 2013 |
Externally published | Yes |
Keywords
- DNA polymerase beta
- Fidelity of DNA synthesis
- Meiosis
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology