title: Cleavage factor I links transcription termination to DNA damage response and genome integrity maintenance in Saccharomyces cerevisiae.
abstract: 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.
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla-CSIC, Sevilla, Spain.
authors.forename: Hélène
authors.initials: H
authors.lastname: Gaillard
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla-CSIC, Sevilla, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Aguilera
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D004249:DNA Damage / Q000235:genetics* / Q000528:radiation effects; D004261:DNA Replication / Q000235:genetics; D042822:Genomic Instability; D012322:RNA Precursors / Q000235:genetics*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014466:Ultraviolet Rays; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C569777:CF IA protein, S cerevisiae; D012322:RNA Precursors; D029701:Saccharomyces cerevisiae Proteins; D039221:mRNA Cleavage and Polyadenylation Factors