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A critical role for Dna2 at unwound telomeres

Lookup NU author(s): Dr Marta Markiewicz-Potoczny, Professor David Lydall

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2018 Markiewicz-Potoczny et al. Dna2 is a nuclease and helicase that functions redundantly with other proteins in Okazaki fragment processing, doublestrand break resection, and checkpoint kinase activation. Dna2 is an essential enzyme, required for yeast and mammalian cell viability. Here, we report that numerous mutations affecting the DNA damage checkpoint suppress dna2Δ lethality in Saccharomyces cerevisiae. dna2Δ cells are also suppressed by deletion of helicases PIF1 and MPH1, and by deletion of POL32, a subunit of DNA polymerase d. All dna2Δ cells are temperature sensitive, have telomere length defects, and low levels of telomeric 39 single-stranded DNA (ssDNA). Interestingly, Rfa1, a subunit of the major ssDNA binding protein RPA, and the telomere-specific ssDNA binding protein Cdc13, often colocalize in dna2Δ cells. This suggests that telomeric defects often occur in dna2Δ cells. There are several plausible explanations for why the most critical function of Dna2 is at telomeres. Telomeres modulate the DNA damage response at chromosome ends, inhibiting resection, ligation, and cell-cycle arrest. We suggest that Dna2 nuclease activity contributes to modulating the DNA damage response at telomeres by removing telomeric C-rich ssDNA and thus preventing checkpoint activation.


Publication metadata

Author(s): Markiewicz-Potoczny M, Lisby M, Lydall D

Publication type: Article

Publication status: Published

Journal: Genetics

Year: 2018

Volume: 209

Issue: 1

Pages: 129-141

Print publication date: 01/05/2018

Online publication date: 01/05/2018

Acceptance date: 09/03/2018

Date deposited: 14/06/2018

ISSN (print): 0016-6731

ISSN (electronic): 1943-2631

Publisher: Genetics Society of America

URL: https://doi.org/10.1534/genetics.118.300809

DOI: 10.1534/genetics.118.300809


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