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Upregulation of dNT...
Upregulation of dNTP Levels After Telomerase Inactivation Influences Telomerase-Independent Telomere Maintenance Pathway Choice in Saccharomyces cerevisiae
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van Mourik, Paula M (author)
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de Jong, Jannie (author)
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- Sharma, Sushma (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik,Andrei Chabes
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Kavšek, Alan (author)
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- Chabes, Andrei (author)
- Umeå universitet,Institutionen för medicinsk kemi och biofysik,Molekylär Infektionsmedicin, Sverige (MIMS),Andrei Chabes
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Chang, Michael (author)
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(creator_code:org_t)
- 2018-08-01
- 2018
- English.
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In: G3. - : Oxford University Press (OUP). - 2160-1836. ; 8:8, s. 2551-2558
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https://umu.diva-por... (primary) (Raw object)
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Saccharomyces cerevisiae
- dNTP levels
- survivors
- telomerase-independent telomere maintenance
- telomeres
Publication and Content Type
- ref (subject category)
- art (subject category)
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