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- Title
G-quadruplex-induced instability during leading-strand replication.
- Authors
Lopes, Judith; Piazza, Aurèle; Bermejo, Rodrigo; Kriegsman, Barry; Colosio, Arianna; Teulade-Fichou, Marie-Paule; Foiani, Marco; Nicolas, Alain
- Abstract
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.
- Publication
The EMBO journal, 2011, Vol 30, Issue 19, p4033
- ISSN
1460-2075
- Publication type
Journal Article
- DOI
10.1038/emboj.2011.316