Browse by author
Lookup NU author(s): Dr Marta Markiewicz-Potoczny,
Professor David Lydall
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 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.
Author(s): Markiewicz-Potoczny M, Lisby M, Lydall D
Publication type: Article
Publication status: Published
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
Altmetrics provided by Altmetric