The long-term objective of the proposed research is to determine if Pol-B is essential for meiosis, and to delineate its role in this process. According to current models, DNA synthesis takes place during pre-meiotic S-phase, resulting in four instead of two copies of each chromosome. DNA synthesis occurs during the zygotene substage of prophase I, and is hypothesized to play a role in the pairing process. During pachynema, DNA synthesis takes place most likely to repair gaps resulting from the double-strand breaks and branch migration that complete the process of homologous recombination, and also to fill in gaps during gene conversion. Each of these DNA synthesis events requires a DNA polymerase and its associated proteins. The applicants have recently provided evidence for a role for DNA polymerase B (Pol-B) in meiosis.
The specific aims are: to test the hypothesis that DNA polymerase B is critical for meiosis and to identify proteins from mouse testis, which interact with Pol-B. To test these hypotheses, the Pol-B gene will be deleted from mouse testis using gene targeting technology, and it will be determined if the mice display abnormal meiosis. Testicular proteins that interact with Pol-B in two hybrid screens will be characterized to make conclusions about their function.
| Sterling, Catherine H; Sweasy, Joann B (2006) DNA polymerase 4 of Saccharomyces cerevisiae is important for accurate repair of methyl-methanesulfonate-induced DNA damage. Genetics 172:89-98 |
| Fotiadou, Poppy; Henegariu, Octavian; Sweasy, Joann B (2004) DNA polymerase beta interacts with TRF2 and induces telomere dysfunction in a murine mammary cell line. Cancer Res 64:3830-7 |
| Jonason, A S; Baker, S M; Sweasy, J B (2001) Interaction of DNA polymerase beta with GRIP1 during meiosis. Chromosoma 110:402-10 |
