The 3' processing factor CstF functions in the DNA repair response.
Following DNA damage, mRNA levels decrease, reflecting a coordinated interaction of the DNA repair, transcription and RNA processing machineries. In this study, we provide evidence that transcription and polyadenylation of mRNA precursors are both affected in vivo by UV treatment. We next show that the polyadenylation factor CstF, plays a direct role in the DNA damage response. Cells with reduced levels of CstF display decreased viability following UV treatment, reduced ability to ubiquitinate RNA polymerase II (RNAP II), and defects in repair of DNA damage. Furthermore, we show that CstF, RNAP II and BARD1 are all found at sites of repaired DNA. Our results indicate that CstF plays an active role in the response to DNA damage, providing a link between transcription-coupled RNA processing and DNA repair.
Mirkin
Nurit
N
Chemistry Department, Hunter College, City University of New York, New York, NY 10027, USA.
Fonseca
Danae
D
Mohammed
Samia
S
Cevher
Murat A
MA
Manley
James L
JL
Kleiman
Frida E
FE
D039241:Cleavage Stimulation Factor / Q000502:physiology*; D004249:DNA Damage; D004260:DNA Repair; D006367:HeLa Cells; D006801:Humans; D026723:Polyadenylation; D012319:RNA Polymerase II / Q000378:metabolism; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014466:Ultraviolet Rays
D039241:Cleavage Stimulation Factor; D025521:Tumor Suppressor Proteins; D025801:Ubiquitin; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases; D012319:RNA Polymerase II