A Tripartite Approach to Elucidate Rdh54 function

Columbia University Health Sciences, New York NY

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Abstract

DESCRIPTION (provided by applicant): Members of the RAD52 epistasis group are necessary for maintaining genomic integrity. Through homologous recombination (HR), RAD52 group proteins faithfully repair lesions caused by spontaneous or induced DNA damage. Two members of this group, Rad54 and Rdh54, are homologs and Swi/Snf-like ATPases with partially overlapping functions in vivo. Rad54 is thought to act during HR, during strand invasion and D-loop formation. Although Rdh54 has similar activity in vitro, its diploid-specific phenotype and role in checkpoint adaptation suggest additional functions for Rdh54. Localization of Rdh54 and Rad54 when fused to GFP tags has provided clues into the roles of these proteins in vivo. Rdh54 localizes constitutively to kinetochores and partially relocalizes to DNA repair foci post-DNA damage in both haploid and diploid cells, whereas Rad54 localizes solely to repair foci. These experiments aim to obtain clues into the function of Rdh54 from three approaches. Further study into the non-recombination functions of Rdh54 may reveal a role in the communication between the recombination process and the cellular components controlling chromosome segregation.