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.

G-quadruplex-induced instability during leading-strand replication / J. Lopes, A. Piazza, R. Bermejo, B. Kriegsman, A. Colosio, M.P. Teulade-Fichou, M. Foiani, A. Nicolas. - In: EMBO JOURNAL. - ISSN 0261-4189. - 30:19(2011), pp. 4033-4046.

G-quadruplex-induced instability during leading-strand replication

M. Foiani
Penultimo
;
2011

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.
English
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 BIO/11 - Biologia Molecolare
Articolo
Sì, ma tipo non specificato
2011
30
19
4033
4046
Pubblicato
Periodico con rilevanza internazionale
Pubmed
info:eu-repo/semantics/article
G-quadruplex-induced instability during leading-strand replication / J. Lopes, A. Piazza, R. Bermejo, B. Kriegsman, A. Colosio, M.P. Teulade-Fichou, M. Foiani, A. Nicolas. - In: EMBO JOURNAL. - ISSN 0261-4189. - 30:19(2011), pp. 4033-4046.
none
Prodotti della ricerca::01 - Articolo su periodico
8
262
Article (author)
si
J. Lopes, A. Piazza, R. Bermejo, B. Kriegsman, A. Colosio, M.P. Teulade-Fichou, M. Foiani, A. Nicolas
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/171152
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