Systematic yeast synthetic lethal and synthetic dosage lethal screens identify genes required for chromosome segregation

被引:101
作者
Measday, V
Baetz, K
Guzzo, J
Yuen, K
Kwok, T
Sheikh, B
Ding, HM
Ueta, R
Hoac, T
Cheng, B
Pot, I
Tong, A
Yamaguchi-Iwai, Y
Boone, C
Hieter, P
Andrews, B
机构
[1] Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON M5S 1A8, Canada
[2] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5G 1L6, Canada
[3] Kyoto Univ, Div Integrated Life Sci, Dept Appl Mol Biol, Grad Sch Biostudies,Sakyo Ku, Kyoto 6068502, Japan
[4] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa Inst Syst Biol, Ottawa, ON K1H 8M5, Canada
[5] Univ British Columbia, Ctr Met Proc Engn, Wine Res Ctr, Vancouver, BC V6T 1Z4, Canada
[6] Univ British Columbia, Ctr Met Proc Engn, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada
关键词
chromosome stability; synthetic genetic array; kinetochore;
D O I
10.1073/pnas.0503504102
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Accurate chromosome segregation requires the execution and coordination of many processes during mitosis, including DNA replication, sister chromatid cohesion, and attachment of chromosomes to spindle microtubules via the kinetochore complex. Additional pathways are likely involved because faithful chromosome segregation also requires proteins that are not physically associated with the chromosome. Using kinetochore mutants as a starting point, we have identified genes with roles in chromosome stability by performing genome-wide screens employing synthetic genetic array methodology. Two genetic approaches (a series of synthetic lethal and synthetic dosage lethal screens) isolated 211 nonessential deletion mutants that were unable to tolerate defects in kinetochore function. Although synthetic lethality and synthetic dosage lethality are thought to be based upon similar genetic principles, we found that the majority of interactions associated with these two screens were nonoverlapping. To functionally characterize genes isolated in our screens, a secondary screen was performed to assess defects in chromosome segregation. Genes identified in the secondary screen were enriched for genes with known roles in chromosome segregation. We also uncovered genes with diverse functions, such as RCS1, which encodes an iron transcription factor. RCS1 was one of a small group of genes identified in all three screens, and we used genetic and cell biological assays to confirm that it is required for chromosome stability. Our study shows that systematic genetic screens are a powerful means to discover roles for uncharacterized genes and genes with alternative functions in chromosome maintenance that may not be discovered by using proteornics approaches.
引用
收藏
页码:13956 / 13961
页数:6
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