IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Two types of DNA lesions differentially affect alternative splicing
Autor/es:
LUCIANA E. GIONO; NICOLÁS NIETO MORENO; ADRIÁN CAMBINDO BOTTO; MANUEL J. MUÑOZ; ALBERTO R. KORNBLIHTT
Lugar:
Rosario, Santa Fé
Reunión:
Congreso; L Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2014
Institución organizadora:
Sociedad Argentina de Investigación en Bioquímica y Biología Molecular
Resumen:
UV radiation is a constant source of damage to DNA and other cellular components. This activates a network of specific signaling pathways that regulates transcription and alternative pre-mRNA splicing (AS), among other cellular processes. Deficiencies in these pathways lead to mutation accumulation and, likely, cancer. We have previously shown that UV irradiation promotes hyperphosphorylation of the carboxy terminal domain of RNA polymerase II, slowing down transcriptional elongation and therefore affecting the AS of several genes. UV radiation generates two main types of DNA lesions, the photoproducts cyclobutane pyrimidine dimers (CPDs) and 6-4 pyrimidine-pyrimidones [(6-4)PPs] that differ in terms of the distortion generated on the DNA double helix, their half-life, and the initial recognition by proteins of the Nucleotide Excision Repair pathway. Here, we used two approaches to dissect the effect of each type of lesion on alternative splicing: 1) two xenogenic lesion-specific DNA photolyases, absent from human cells, that selectively repair CPDs or (6-4)PPs; 2) irradiation with UVB (305 nm) and UVC (254 nm) that differ in the relative proportion of CPD and (6-4)PPs generated. Using these tools, we show that DNA damage in itself is sufficient to cause changes in AS. Moreover, UV-induced lesions, CPDs and (6-4)PPs differentially affect individual AS events.