Poster abstracts

Poster number 15 submitted by Randal Soukup

Characterizing the Role of MSH4-MSH5 in Meiotic Homologous Recombination

Randal J. Soukup (Molecular virology, immunology and medical genetics, The Ohio State University), Richard A. Fishel (Molecular virology, immunology and medical genetics, The Ohio State University)

Abstract:
DNA double strand breaks (DSBs) are a unique problem for cells to address. Unlike most DNA repair pathways, which make use of local complementary DNA as template to correct the incorrect DNA site, DSB pathways must either locate a homologous chromosome to use as template for accurate repair or simply ligate the broken ends to one another. The severity of this DNA damage can cause cell death when unrepaired, and when repaired can form genome rearrangements (translocations, deletions, fusions). These genome rearrangements are often found in many types of cancer, also, mutations in DSB repair genes are commonly found in tumor samples and are often sources of hereditary cancer. Oddly enough in meiotic cells hundreds of DSBs are induced throughout the genome in the onset of Prophase I. These breaks are primarily repaired through homologous recombination and serve two purposes: 1. Promote exchange of genetic information between parental chromosomes and 2. Some crossover points will mature into chiasmata which allow for specific separation of non-sister homologous chromosomes in meiosis I. While the mechanism for mitotic homologous recombination is well understood, the mechanism for meiotic DSB repair is still being uncovered. Evidence from genetic, cellular, and biophysical studies shows that MSH4-MSH5, a MutS homolog, is involved in meiotic homologous recombination. Our group has previously shown MSH4-MSH5 specifically recognizes Holliday Junctions in vitro. In an effort to determine the role MSH4-MSH5 plays upon recognizing Holliday Junction we compare the rate of branch migration with and without purified MSH4-MSH5. We report that MSH4-MSH5 is able to increase the speed of branch migration two-fold. We postulate that this increase is due to MSH4-MSH5 locking the Holliday Junction in a conformation which enhances movement of the branch point.

Keywords: Homologous Recombination, Meiosis, Branch Migration