Cleavage Factor I Links Transcription Termination to DNA Damage Response and Genome Integrity Maintenance in Saccharomyces cerevisiae

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. © 2014 gaillard,aguilera.