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

Phong Lan Thao Tran; Thomas J. Pohl; Chi Fu Chen; Angela Chan; Sebastian Pott; Virginia A. Zakian

doi:10.1038/ncomms15025

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

Phong Lan Thao Tran, Thomas J. Pohl, Chi Fu Chen, Angela Chan, Sebastian Pott, Virginia A. Zakian

Molecular Biology

Research output: Contribution to journal › Article › peer-review

77 Scopus citations

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.

Original language	English (US)
Article number	15025
Journal	Nature communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms15025
State	Published - 2017

All Science Journal Classification (ASJC) codes

Physics and Astronomy(all)
Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)

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title = "PIF1 family DNA helicases suppress R-loop mediated genome instability at tRNA genes",

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.",

author = "Tran, {Phong Lan Thao} and Pohl, {Thomas J.} and Chen, {Chi Fu} and Angela Chan and Sebastian Pott and Zakian, {Virginia A.}",

note = "Funding Information: We thank Duncan Smith for sharing data prior to submission, as well as Chris Webb and Cindy Follonier for helpful discussions. The laboratory of V.A.Z. is funded by National Institutes of Health grant 1R35GM118279. P.L.T.T., C.-F.C. and T.J.P. are supported by fellowships from EMBO, NJCCR, FORD Foundation and Burroughs Wellcome. Publisher Copyright: {\textcopyright} The Author(s) 2017.",

year = "2017",

doi = "10.1038/ncomms15025",

language = "English (US)",

volume = "8",

journal = "Nature Communications",

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T1 - PIF1 family DNA helicases suppress R-loop mediated genome instability at tRNA genes

AU - Tran, Phong Lan Thao

AU - Pohl, Thomas J.

AU - Chen, Chi Fu

AU - Chan, Angela

AU - Pott, Sebastian

AU - Zakian, Virginia A.

N1 - Funding Information: We thank Duncan Smith for sharing data prior to submission, as well as Chris Webb and Cindy Follonier for helpful discussions. The laboratory of V.A.Z. is funded by National Institutes of Health grant 1R35GM118279. P.L.T.T., C.-F.C. and T.J.P. are supported by fellowships from EMBO, NJCCR, FORD Foundation and Burroughs Wellcome. Publisher Copyright: © The Author(s) 2017.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

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

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