DNA POLYMERASE BETA AND MEIOSIS

Yale University, New Haven CT

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Abstract

DESCRIPTION (Adapted from investigator's abstract): 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.