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

Author(s): Tran, Phong Lan Thao; Pohl, Thomas J; Chen, Chi-Fu; Chan, Angela; Pott, Sebastian; et al

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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.
Publication Date: 21-Apr-2017
Citation: Tran, Phong Lan Thao, Pohl, Thomas J, Chen, Chi-Fu, Chan, Angela, Pott, Sebastian, Zakian, Virginia A. (2017). PIF1 family DNA helicases suppress R-loop mediated genome instability at tRNA genes. Nature Communications, 8 (15025 - 15025). doi:10.1038/ncomms15025
DOI: doi:10.1038/ncomms15025
ISSN: 2041-1723
EISSN: 2041-1723
Pages: 15025 - 15025
Language: eng
Type of Material: Journal Article
Journal/Proceeding Title: Nature Communications
Version: Final published version. This is an open access article.

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