G-quadruplexes are four-stranded nucleic acid structures whose biological functions remain poorly understood. In the yeast S. cerevisiae, we report that G-quadruplexes form and, if not properly processed, pose a specific challenge to replication. We show that the G-quadruplex-prone CEB1 tandem array is tolerated when inserted near ARS305 replication origin in wild-type cells but is very frequently destabilized upon treatment with the potent Phen-DC(3) G-quadruplex ligand, or in the absence of the G-quadruplex-unwinding Pif1 helicase, only when the G-rich strand is the template of leading-strand replication. The orientation-dependent instability is associated with the formation of Rad51-Rad52-dependent X-shaped intermediates during replication detected by two-dimensional (2D) gels, and relies on the presence of intact G-quadruplex motifs in CEB1 and on the activity of ARS305. The asymmetrical behaviour of G-quadruplex prone sequences during replication has implications for their evolutionary dynamics within genomes, including the maintenance of G-rich telomeres.
|Titolo:||G-quadruplex-induced instability during leading-strand replication|
FOIANI, MARCO (Penultimo)
|Parole Chiave:||G-Quadruplexes ; Rad51 Recombinase ; Saccharomyces cerevisiae Proteins ; Nucleic Acid Conformation ; Rad52 DNA Repair and Recombination Protein ; Saccharomyces cerevisiae; Nucleotidyltransferases ; DNA Helicases ; Models, Genetic ; Recombination, Genetic ; Cell Cycle ; DNA Replication ; Genomics|
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
|Data di pubblicazione:||2011|
|Digital Object Identifier (DOI):||10.1038/emboj.2011.316|
|Appare nelle tipologie:||01 - Articolo su periodico|