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
Date Published2017 04 21
KeywordsDNA Damage, DNA Helicases, DNA Replication, DNA, Fungal, Gene Expression Regulation, Fungal, Genome, Fungal, Genomic Instability, Nucleic Acid Conformation, Protein Binding, Recombinational DNA Repair, RNA, Transfer, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins

<p>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.</p>

Alternate JournalNat Commun
PubMed ID28429714
PubMed Central IDPMC5413955
Grant ListR01 GM026938 / GM / NIGMS NIH HHS / United States
R35 GM118279 / GM / NIGMS NIH HHS / United States