My goal is to understand the mechanisms that coordinate higher order chromosome structure with formation and repair of DNA double-stranded breaks (DSBs) during meiosis, the cell division program that produces haploid gametes from diploid germ cells. Control of chromosome structure is crucial in meiosis, where DSBs are intentionally induced and repaired to form chiasmata linking chromosomes in preparation for homolog separation. The C. elegans CHK-2 protein has been identified as a key coordinator of chromosome structure, pairing, and initiation of DSB formation in meiosis. CHK-2 is an ortholog of the mammalian DNA damage checkpoint kinase Chk2, which is mutated in the familial cancer syndrome Li Fraumeni. This proposal outlines my strategy to reveal the network of control by which CHK-2 coordinates meiotic chromosome organization and DNA metabolic events to ensure genomic integrity. I will identify CHK-2 binding proteins and phosphorylation targets and determine their meiotic functions. I will test hypotheses about the mechanisms CHK-2 employs in chromosome reorganization, pairing and DSB formation. I will engineer an inactivatable CHK-2 enzyme to investigate possible CHK-2 roles after DSB formation in meiosis. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM079015-03
Application #
7491481
Study Section
Special Emphasis Panel (ZRG1-F08-G (20))
Program Officer
Haynes, Susan R
Project Start
2006-09-16
Project End
2009-04-24
Budget Start
2008-09-16
Budget End
2009-04-24
Support Year
3
Fiscal Year
2008
Total Cost
$33,418
Indirect Cost
Name
Stanford University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305