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Alain Nicolas — Minisatellite instability and G-quadruplexes

Speaker :

Alain Nicolas, Dynamique de l’Information Génétique : Bases Fondamentales et Cancer, Institut Curie, Paris

Where :

When :

Mercredi 8 Avril 2009 à 11:00

Title :

Minisatellite instability and G-quadruplexes

Abstract :

In Saccharomyces cerevisiae, the Pif1 5’-3’ DNA helicase is involved in the maintenance of both nuclear and mitochondrial genomes, but its role in these processes is still poorly understood. We found that the absence of Pif1 specifically promotes genetic instability of alleles of the G/C rich human minisatellite CEB1 inserted in the yeast genome, but not of other tandem repeats. We also conducted in vitro analyses. The G/C rich CEB1 repeat is able to form G-quadruplexes structures and Pif1 helicase unwinds these structures efficiently. Finally, we constructed synthetic CEB1 minisatellites mutated for several guanines such that it is unable to form G-quadruplexes structures in vitro and tested their stability in vivo. They were no longer destabilized in pif1Δ cells. We conclude that the instability of the natural hCEB1 minisatellite in pif1∆ cells depends on G-quadruplex-forming sequences and that the yeast Pif1 helicase processes these structures in vitro and in vivo.

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