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G‐quadruplex‐induced instability during leading‐strand replication
Author(s) -
Lopes Judith,
Piazza Aurèle,
Bermejo Rodrigo,
Kriegsman Barry,
Colosio Arianna,
TeuladeFichou MariePaule,
Foiani Marco,
Nicolas Alain
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.316
Subject(s) - biology , replication (statistics) , genome instability , g quadruplex , dna replication , microbiology and biotechnology , genetics , instability , dna , virology , dna damage , physics , mechanics
G‐quadruplexes are four‐stranded nucleic acid structures whose biological functions remain poorly understood. In the yeast S. cerevisia e, 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.