TY - JOUR T1 - Pif1-family helicases cooperate to suppress widespread replication fork arrest at tRNA genes JF - bioRxiv DO - 10.1101/082008 SP - 082008 AU - Joseph S. Osmundson AU - Jayashree Kumar AU - Rani Yeung AU - Duncan J. Smith Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/10/19/082008.abstract N2 - Saccharomyces cerevisiae encodes two distinct Pif1-family helicases – Pif1 and Rrm3 – which have been reported to play distinct roles in numerous nuclear processes. Here, we systematically characterize the roles of Pif1 helicases in replisome progression and lagging-strand synthesis in S. cerevisiae. We demonstrate that either Pif1 or Rrm3 redundantly stimulate strand-displacement by DNA polymerase δ 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; consistent with this observation, we find that head-on collisions between tRNA transcription and replisome progression are under-represented in the S. cerevisiae genome. Further, we demonstrate that tRNA-mediated arrest is R-loop independent, and propose that replisome arrest and DNA damage are mechanistically separable. ER -