Pif1-family helicases cooperate to suppress widespread replication fork arrest at tRNA genes
Autor: | Duncan J. Smith, Joseph Osmundson, Jayashree Kumar, Rani Yeung |
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Rok vydání: | 2016 |
Předmět: |
0303 health sciences
biology DNA polymerase Saccharomyces cerevisiae Helicase biology.organism_classification TRNA transcription Cell biology Replication fork arrest 03 medical and health sciences 0302 clinical medicine Transfer RNA biology.protein Replisome Gene 030217 neurology & neurosurgery 030304 developmental biology |
DOI: | 10.1101/082008 |
Popis: | Saccharomyces cerevisiaeencodes 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 inS. cerevisiae. We demonstrate that either Pif1 or Rrm3 redundantly stimulate strand-displacement by DNA polymerase δ during lagging-strand synthesis. By analyzing replisome mobility inpif1andrrm3mutants, 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 theS. cerevisiaegenome. Further, we demonstrate that tRNA-mediated arrest is R-loop independent, and propose that replisome arrest and DNA damage are mechanistically separable. |
Databáze: | OpenAIRE |
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