Upregulation of dNTP Levels After Telomerase Inactivation Influences Telomerase-Independent Telomere Maintenance Pathway Choice in Saccharomyces cerevisiae

G3: Genes, Genomes, Genetics

article

Paula M. van Mourik¹  Jannie de Jong¹  Sushma Sharma²  Alan Kavšek¹  Andrei Chabes²  Michael Chang¹ 

[1] European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, the Netherlands;Department of Medical Biochemistry and Biophysics,Umeå University, SE 901 87 Umeå, Sweden;Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, SE 901 87 Umeå,Sweden

关键词: Saccharomyces cerevisiae;    telomeres;    telomerase-independent telomere maintenance;    survivors;    dNTP levels;   

DOI  :  10.1534/g3.118.200280

学科分类：社会科学、人文和艺术（综合）

来源: Genetics Society of America

【 摘 要 】

In 10–15% of cancers, telomere length is maintained by a telomerase-independent, recombination-mediated pathway called alternative lengthening of telomeres (ALT). ALT mechanisms were first seen, and have been best studied, in telomerase-null Saccharomyces cerevisiae cells called “survivors”. There are two main types of survivors. Type I survivors amplify Y′ subtelomeric elements while type II survivors, similar to the majority of human ALT cells, amplify the terminal telomeric repeats. Both types of survivors require Rad52 , a key homologous recombination protein, and Pol32 , a non-essential subunit of DNA polymerase δ. A number of additional proteins have been reported to be important for either type I or type II survivor formation, but it is still unclear how these two pathways maintain telomeres. In this study, we performed a genome-wide screen to identify novel genes that are important for the formation of type II ALT-like survivors. We identified 23 genes that disrupt type II survivor formation when deleted. 17 of these genes had not been previously reported to do so. Several of these genes ( DUN1 , CCR4 , and MOT2 ) are known to be involved in the regulation of dNTP levels. We find that dNTP levels are elevated early after telomerase inactivation and that this increase favors the formation of type II survivors.

【 授权许可】

CC BY|CC BY-NC