The Bur1 cyclin-dependent kinase regulates telomere length in Saccharomyces cerevisiae

被引:4
|
作者
Connelly, Carla J. [1 ]
Vidal-Cardenas, Sofia [1 ,2 ]
Goldsmith, Stephanie [1 ,3 ]
Greider, Carol W. [1 ,4 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, 603 PCTB,725 N Wolfe St, Baltimore, MD 21205 USA
[2] Exelixis Inc, Alameda, CA USA
[3] Cold Spring Harbor Lab, Cold Spring Harbor, NY USA
[4] Univ Calif Santa Cruz, Dept Mol Cell & Dev Biol, Santa Cruz, CA 95064 USA
关键词
Bur1; Bur2; kinase; telomere length equilibrium; DNA-DAMAGE RESPONSE; GENOME-WIDE SCREEN; DYSKERATOSIS-CONGENITA; INDEPENDENT FUNCTIONS; HISTONE METHYLATION; TERMINAL DOMAIN; PROTEIN-KINASE; YEAST GENES; COMPLEX; RNA;
D O I
10.1002/yea.3680
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Telomere length regulation is essential for cell viability in eukaryotes. While many pathways that affect telomere length are known, we do not yet have a complete understanding of the mechanism of length regulation. To identify new pathways that might regulate telomere length, we carried out a genetic screen in yeast and identified the cyclin-dependent kinase complex Bur1/2 as a regulator of telomere length. Mutations in either BUR1 cyclin-dependent kinase or the associated BUR2 cyclin resulted in short telomeres. This regulation did not function through the known role of BUR1 in regulating histone modification as bur1 increment set2 increment and bur2 increment set2 increment double mutants rescued cell growth but did not rescue the telomere shortening effects. We found that both bur1 increment and bur2 increment set2 increment were also defective in de novo telomere addition, and deletion of SET2 did also not rescue this elongation defect. The Bur1/2 cyclin-dependent kinase regulates transcription of many genes. We found that TLC1 RNA levels were reduced in bur2 increment set2 increment mutants; however, overexpression of TLC1 restored the transcript levels but did not restore de novo telomere elongation or telomere length. These data suggest that the Bur1/2 kinase plays a role in telomere elongation separate from its role in transcription of telomerase components. Dissecting the role of the Bur1/2 kinase pathway at telomeres will help complete our understanding of the complex network of telomere length regulation.
引用
收藏
页码:177 / 192
页数:16
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