Ultraviolet (UV) light induces DNA-damage checkpoints and mutagenesis, which are involved in cancer protection and tumorigenesis, respectively. How cells identify DNA lesions and convert them to checkpoint-activating structures is a major question. We show that during repair of UV lesions in noncycling cells, Exo1-mediated processing of nucleotide excision repair (NER) intermediates competes with repair DNA synthesis. Impediments of the refilling reaction allow Exo1 to generate extended ssDNA gaps, detectable by electron microscopy, which drive Mec1 kinase activation and will be refilled by long-patch repair synthesis, as shown by DNA combing. We provide evidence that this mechanism may be stimulated by closely opposing UV lesions, represents a strategy to redirect problematic repair intermediates to alternative repair pathways, and may also be extended to physically different DNA damages. Our work has significant implications for understanding the coordination between repair of DNA lesions and checkpoint pathways to preserve genome stability.
Exo1 competes with repair synthesis, converts NER intermediates to long ssDNA gaps, and promotes checkpoint activation / M. Giannattasio, C. Follonier, H. Tourrière, F. Puddu, F. Lazzaro, P. Pasero, M. Lopes, P. Plevani, M. Muzi-Falconi. - In: MOLECULAR CELL. - ISSN 1097-2765. - 40:1(2010 Oct 08), pp. 50-62.
|Titolo:||Exo1 competes with repair synthesis, converts NER intermediates to long ssDNA gaps, and promotes checkpoint activation|
GIANNATTASIO, MICHELE (Primo)
PLEVANI, PAOLO (Penultimo)
MUZI FALCONI, MARCO (Ultimo)
|Parole Chiave:||nucleotide-excision-repair; irradiated escherichia-coli; DNA-damage checkpoint; replication forks; saccharomyces-cerevisiae; H2AX phosphorylation; human-fibroblasts; mismatch repair; human-cells; polymerases|
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
Settore BIO/18 - Genetica
Settore BIO/10 - Biochimica
|Data di pubblicazione:||8-ott-2010|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.molcel.2010.09.004|
|Appare nelle tipologie:||01 - Articolo su periodico|