Pif1-family helicases cooperatively suppress widespread replication-fork arrest at tRNA genes

Joseph S. Osmundson, Jayashree Kumar, Rani Yeung, Duncan J. Smith

Research output: Contribution to journalArticlepeer-review

Abstract

Saccharomyces cerevisiae expresses two Pif1-family helicases - Pif1 and Rrm3 - which have been reported to play distinct roles in numerous nuclear processes. Here, we systematically characterized the roles of Pif1 helicases in replisome progression and lagging-strand synthesis in S. cerevisiae. We demonstrate that either Pif1 or Rrm3 redundantly stimulates strand displacement by DNA polymerase during lagging-strand synthesis. By analyzing replisome mobility in pif1 and rrm3 mutants, we show that Rrm3, with a partially redundant contribution from Pif1, suppresses widespread terminal arrest of the replisome at tRNA genes. Although both head-on and codirectional collisions induce replication-fork arrest at tRNA genes, head-on collisions arrest a higher proportion of replisomes. In agreement with this observation, we found that head-on collisions between tRNA transcription and replication are under-represented in the S. cerevisiae genome. We demonstrate that tRNA-mediated arrest is R-loop independent and propose that replisome arrest and DNA damage are mechanistically separable.

Original languageEnglish (US)
Pages (from-to)162-170
Number of pages9
JournalNature Structural and Molecular Biology
Volume24
Issue number2
DOIs
StatePublished - Feb 1 2017

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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