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Meiotic Recombination and DNA Repair in Drosophila

$453,221FY2002BIONSF

University Of North Carolina At Chapel Hill, Chapel Hill NC

Investigators

Abstract

The mechanisms by which cells repair DNA interstrand crosslinks remain largely unknown. In mammals, the nucleotide excision repair endonuclease XPF-Ercc1 plays a key role in interstrand crosslink repair. This function is conserved in the Drosophila XPF homolog MEI-9. This project concerns the interaction between MEI-9 and a newly identified crosslink repair protein, MUS312. Genetic analyses of mus312 mutants will be done to better understand which repair and recombination pathways require mus312, and to what extent mus312 and mei-9 act in the same pathways. Additional alleles of mus312 will be generated to better understand the MUS312 protein. Both mei-9 and mus312 are also essential for generating meiotic crossovers, and this function will also be studied genetically and molecularly. DNA is under constant attack by both internal and external agents; several chemotherapy agents exert their effects by creating interstrand crosslinks in DNA. The mechanisms by which normal cells repair this type of damage are unknown. The present research seeks to understand the contribution to this repair of two key proteins, MEI-9 and MUS312. These proteins interact physically to carry out this repair process in Drosophila melanogaster.

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