This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Maintenance of genomic integrity is essential for all organisms, and cells respond to DNA damage with a tightly orchestrated sequence of events that coordinates cell cycle arrest and DNA repair. The overall objective of this project is to advance our understanding of this process, using S. cerevisiae as a model system to study the function of Bcp1, an essential protein in yeast. Bcp1 is the fungal homolog of BCCIP, a protein originally identified by its association with tumor suppressor BRCA2, and cell cycle regulator CDKN1A (p21). In human cells, BCCIP promotes cell cycle arrest following DNA damage, and participates in homologous recombination repair in conjunction with BRCA2. To begin to elucidate the role of Bcp1 in the S. cerevisiae DNA damage response, we will examine the hypothesis that Bcp1 localizes to sites of DNA damage and contributes to checkpoint activation leading to cell cycle arrest.
Two Specific Aims are proposed: 1) Analyze Bcp1 localization and association with chromatin-bound protein complexes in cells treated with DNA damaging agents, and define how loss of Bcp1 impacts DNA repair or cell survival and 2) Evaluate a role for Bcp1 in checkpoint activation in response to DNA damage. The results of this study will provide insight as to the biological function of Bcp1 and its contribution to the critically important DNA damage response.
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