A homologous recombination defect affects replication-fork progression in mammalian cells.

Fayza Daboussi , Sylvain Courbet , Simone Benhamou (1) , Patricia Kannouche , Malgorzata Z Zdzienicka , Michelle Debatisse , Bernard S Lopez (2, 3, 4)

1 Unité de Recherches en Epidémiologie des Cancers
2 LG - Laboratoire Gemini
3 FRESNEL - Département Fresnel
4 LMR - Laboratoire d'étude des Mécanismes de la recombinaison

Faithful genome transmission requires a network of pathways coordinating DNA replication to DNA repair and recombination. Here, we used molecular combing to measure the impact of homologous recombination (HR) on the velocity of DNA replication forks. We used three hamster cell lines defective in HR either by overexpression of a RAD51 dominant-negative form, or by a defect in the RAD51 paralogue XRCC2 or the breast tumor suppressor BRCA2. Irrespectively of the type or extent of HR alteration, all three cell lines exhibited a similar reduction in the rate of replication-fork progression, associated with an increase in the density of replication forks. Importantly, this phenotype was completely reversed in complemented derivatives of Xrcc2 and Brca2 mutants. These data reveal a novel role for HR, different from the reactivation of stalled replication forks, which may play an important role in genome stability and thus in tumor protection.

Domaines: Cancer

Fayza Daboussi, Sylvain Courbet, Simone Benhamou, Patricia Kannouche, Malgorzata Z Zdzienicka, et al.. A homologous recombination defect affects replication-fork progression in mammalian cells.. Journal of Cell Science, 2008, 121 (Pt 2), pp.162-6. ⟨10.1242/jcs.010330⟩. ⟨hal-00282471⟩