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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES010995-03
Application #
6525296
Study Section
Mammalian Genetics Study Section (MGN)
Program Officer
Reinlib, Leslie J
Project Start
2000-09-30
Project End
2005-08-31
Budget Start
2002-09-30
Budget End
2003-08-31
Support Year
3
Fiscal Year
2002
Total Cost
$326,683
Indirect Cost
Name
Yale University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
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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