Cleavage factor I links transcription termination to DNA damage response and genome integrity maintenance in Saccharomyces cerevisiae

PLoS Genet. 2014 Mar 6;10(3):e1004203. doi: 10.1371/journal.pgen.1004203. eCollection 2014 Mar.


During transcription, the nascent pre-mRNA undergoes a series of processing steps before being exported to the cytoplasm. The 3'-end processing machinery involves different proteins, this function being crucial to cell growth and viability in eukaryotes. Here, we found that the rna14-1, rna15-1, and hrp1-5 alleles of the cleavage factor I (CFI) cause sensitivity to UV-light in the absence of global genome repair in Saccharomyces cerevisiae. Unexpectedly, CFI mutants were proficient in UV-lesion repair in a transcribed gene. DNA damage checkpoint activation and RNA polymerase II (RNAPII) degradation in response to UV were delayed in CFI-deficient cells, indicating that CFI participates in the DNA damage response (DDR). This is further sustained by the synthetic growth defects observed between rna14-1 and mutants of different repair pathways. Additionally, we found that rna14-1 suffers severe replication progression defects and that a functional G1/S checkpoint becomes essential in avoiding genetic instability in those cells. Thus, CFI function is required to maintain genome integrity and to prevent replication hindrance. These findings reveal a new function for CFI in the DDR and underscore the importance of coordinating transcription termination with replication in the maintenance of genomic stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / genetics
  • DNA Damage / genetics*
  • DNA Damage / radiation effects
  • DNA Replication / genetics
  • Genomic Instability
  • RNA Precursors / genetics*
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription, Genetic*
  • Ultraviolet Rays
  • mRNA Cleavage and Polyadenylation Factors / genetics*
  • mRNA Cleavage and Polyadenylation Factors / metabolism


  • CF IA protein, S cerevisiae
  • RNA Precursors
  • Saccharomyces cerevisiae Proteins
  • mRNA Cleavage and Polyadenylation Factors

Associated data

  • GEO/GSE50947

Grant support

This research was funded by grants from the Spanish Ministry of Economy and Competitiveness (Consolider Ingenio 2010 CSD2007-0015 and BFU2010-16372;, Junta de Andalucía (CVI-4567; and the European Union (FEDER). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.