PIF1 family DNA helicases suppress R-loop mediated genome instability at tRNA genes.

TitlePIF1 family DNA helicases suppress R-loop mediated genome instability at tRNA genes.
Publication TypeJournal Article
Year of Publication2017
AuthorsTran, PLan Thao, Pohl, TJ, Chen, C-F, Chan, A, Pott, S, Zakian, VA
JournalNat Commun
Volume8
Pagination15025
Date Published2017 Apr 21
ISSN2041-1723
Abstract

Saccharomyces cerevisiae encodes two Pif1 family DNA helicases, Pif1 and Rrm3. Rrm3 promotes DNA replication past stable protein complexes at tRNA genes (tDNAs). We identify a new role for the Pif1 helicase: promotion of replication and suppression of DNA damage at tDNAs. Pif1 binds multiple tDNAs, and this binding is higher in rrm3Δ cells. Accumulation of replication intermediates and DNA damage at tDNAs is higher in pif1Δ rrm3Δ than in rrm3Δ cells. DNA damage at tDNAs in the absence of these helicases is suppressed by destabilizing R-loops while Pif1 and Rrm3 binding to tDNAs is increased upon R-loop stabilization. We propose that Rrm3 and Pif1 promote genome stability at tDNAs by displacing the stable multi-protein transcription complex and by removing R-loops. Thus, we identify tDNAs as a new source of R-loop-mediated DNA damage. Given their large number and high transcription rate, tDNAs may be a potent source of genome instability.

DOI10.1038/ncomms15025
Alternate JournalNat Commun
PubMed ID28429714