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First published online 18 December 2007
doi: 10.1242/jcs.010330

Journal of Cell Science 121, 162-166 (2008)
Published by The Company of Biologists 2008
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Short Report

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

Fayza Daboussi1, Sylvain Courbet2, Simone Benhamou3, Patricia Kannouche3, Malgorzata Z. Zdzienicka4, Michelle Debatisse2 and Bernard S. Lopez1,*

1 UMR 217 CNRS, Institut de Radiobiologie Cellulaire et Moléculaire, 18 route du panorama, 92265, Fontenay aux Roses, Cédex, France
2 UMR 7147 CNRS/Institut Curie, 26 rue d'Ulm, 75 248, Paris Cédex 05, France
3 FRE 2939, Institut Gustave Roussy, 94800, Villejuif, France
4 Department of Molecular Cell Genetics, Nicolaus-Copernicus-University in Torun, ul. Sklodowskiej-Curie 9, 85-094 Bydgoszcz, Poland

* Author for correspondence (e-mail: bernard.lopez{at}cea.fr)

Accepted 9 October 2007

Summary

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.

Key words: Homologous recombination, Replication, Mammalian cells, Breast cancer, Unchallenged cells






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