KORNBLIHTT Alberto Rodolfo
Major roles of pyrimidine dimers, nucleotide excision repair and ATR in the alternative splicing response to UV irradiation.
MUÑOZ, M. J.; NIETO MORENO, N.; GIONO, L.; CAMBINDO BOTTO, A. E.; DUJARDIN, G.; BASTIANELLO, G.; LAVORE, S.; TORRES-MÉNDEZ, A.; MENCK, C. F. M.; BLENCOWE, B.; IRIMIA, M.; FOIANI, M.; KORNBLIHTT, A. R.
Año: 2017 vol. 12 p. 2868 - 2868
We have previously found that UV irradiation pro-motes RNA polymerase II (RNAPII) hyperphosphory-lation and subsequent changes in alternative splicing(AS). We show now that UV-induced DNA damage isnot only necessary but sufficient to trigger the ASresponse and that photolyase-mediated removal ofthe most abundant class of pyrimidine dimers (PDs)abrogates the global response to UV. We demon-strate that, in keratinocytes, RNAPII is the target,but not a sensor, of the signaling cascade initiatedby PDs. The UV effect is enhanced by inhibition ofgap-filling DNA synthesis, the last step in the nucleo-tide excision repair pathway (NER), and reduced bythe absence of XPE, the main NER sensor of PDs.The mechanism involves activation of the proteinkinase ATR that mediates the UV-induced RNAPII hy-perphosphorylation. Our results define the sequenceUV-PDs-NER-ATR-RNAPII-AS as a pathway linkingDNA damage repair to the control of both RNAPIIphosphorylation and AS regulation.