Friday February 29 2008
CEA
Cancerology research: evidence that helicase Srs2 protein promotes genome stability
CEA
The Srs2 protein possesses all the biochemical activities necessary to prevent ‘crossovers’, or DNA fragment exchanges between chromosomes, from forming during one of the DNA strand break repair processes – homologous recombination. Srs2 therefore plays a pivotal role in maintaining genome stability and defending the cell against cancer.
This result was achieved through a combined research effort pairing a “Molecular interactions and cancer” team led by Eric Le Cam from the Gustave Roussy Institute -CNRS-Paris Sud University joint research unit UMR8126 with a team led by Xavier Veaute from CEA-CNRS joint research unit UMR217, the “Institute of Cellular and Molecular Radiation Biology”. The work was recently published in the 31 January 2008 issue of Molecular Cell.
Homologous recombination is a process able to repair single-strand and double-strand DNA breaks caused by stressors such as ionising radiation. This means it plays a central role in maintaining genome integrity. However, there are times when recombination between homologous sequences can also involve crossovers liable to lead to chromosomal rearrangements that may trigger cancer. Therefore, crossovers need to be kept to a minimum.
Two teams, one led by Eric Le Cam from the Gustave Roussy Institute, the other led by Xavier Veaute from the CEA’s Fontenay-aux-Roses centre, had previously demonstrated the role played by Srs2 helicase in Saccharomyces cerevisiae yeast in the early regulation of homologous recombination. Other genetics research suggested that Srs2 may also be involved in preventing crossovers. In the work that has just been published, the two teams show that Srs2 possesses all the functional activities needed to enable DNA breaks to be repaired via a pathway that prevents the formation of crossovers, thereby helping to maintain genome stability. The number of crossovers is highly regulated in humans too. Upcoming research will be directed towards determining whether the mechanism identified in yeast is also present in human cells.
This research was partly funded by the National Cancer Institute of France (INCa), the French Agency for Research (ANR), the French Association for Anti-Cancer Research (ARC) and the Ligue contre le cancer.
Article reference:
Dupaigne P, Le Breton C, Fabre F, Gangloff S, Le Cam E and Veaute X.
The Srs2 Helicase Activity Is Stimulated by Rad51 Filaments on dsDNA: Implications for Crossover Incidence during Mitotic Recombination. Mol Cell. 2008 Feb 1;29(2):243-54
Research teams – references:
Laboratoire de Microscopie Moléculaire et Cellulaire – CNRS UMR8126 « Interactions Moléculaires et cancer » - Institut Gustave Roussy – 94805 Villejuif.
Laboratoire d’Etudes de la Réparation de l’ADN – UMR217 – CNRS/CEA - 92265 Fontenay-aux-Roses.
Légende : Srs2 déroule l'ADN double brin couvert de Rad51