comparative genome-wide screening identifies a conserved doxorubicin repair network that is diploid specific in saccharomyces cerevisiae比较全基因组筛选识别守恒的阿霉素修复网络,是二倍体具体在酿酒酵母.pdfVIP

Comparative Genome-Wide Screening Identifies a Conserved Doxorubicin Repair Network That Is Diploid Specific in Saccharomyces cerevisiae 1 2 2 1 Tammy J. Westmoreland , Sajith M. Wickramasekara , Andrew Y. Guo , Alice L. Selim , Tiffany S. 3 3 4 1 1 Winsor , Arno L. Greenleaf , Kimberly L. Blackwell , John A. Olson, Jr. , Jeffrey R. Marks , Craig B. Bennett1* 1 Department of Surgical Sciences, Duke University Medical Center, Durham, North Carolina, United States of America, 2 North Carolina School of Science and Mathematics, Durham, North Carolina, United States of America, 3 Department of Biochemistry, Duke University Medical Center, Durham, North Carolina, United States of America, 4 Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America Abstract The chemotherapeutic doxorubicin (DOX) induces DNA double-strand break (DSB) damage. In order to identify conserved genes that mediate DOX resistance, we screened the Saccharomyces cerevisiae diploid deletion collection and identified 376 deletion strains in which exposure to DOX was lethal or severely reduced growth fitness. This diploid screen identified 5-fold more DOX resistance genes than a comparable screen using the isogenic haploid derivative. Since DSB damage is repaired primarily by homologous recombination in yeast, and haploid cells lack an available DNA homolog in G1 and early S phase, this suggests that our diploid screen may have detected the loss of repair functions in G1 or early S phase prior to complete DNA replication. To test this, we compared the relative DOX sensitivity of 30 diploid deletion mutants identified under our scre