Characterization of homologous recombination induced by replication inhibition in mammalian cells.
To analyze relationships between replication and homologous recombination in mammalian cells, we used replication inhibitors to treat mouse and hamster cell lines containing tandem repeat recombination substrates. In the first step, few double-strand breaks (DSBs) are produced, recombination is slightly increased, but cell lines defective in non-homologous end-joining (NHEJ) affected in ku86 (xrs6) or xrcc4 (XR-1) genes show enhanced sensitivity to replication inhibitors. In the second step, replication inhibition leads to coordinated kinetics of DSB accumulation, Rad51 foci formation and RAD51-dependent gene conversion stimulation. In xrs6 as well as XR-1 cell lines, Rad51 foci accumulate more rapidly compared with their respective controls. We propose that replication inhibition produces DSBs, which are first processed by the NHEJ; then, following DSB accumulation, RAD51 recombination can act.
Saintigny
Y
Y
UMR217 CNRS-CEA and CEA, Direction des Sciences du Vivant, Département de Radiobiologie et Radiopathologie, 60-68 avenue du Général Leclerc, 92 265 Fontenay aux Roses cedex, France.
Delacôte
F
F
Varès
G
G
Petitot
F
F
Lambert
S
S
Averbeck
D
D
Lopez
B S
BS
D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D002460:Cell Line; D020552:Comet Assay; D006224:Cricetinae; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology; D004261:DNA Replication / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000502:physiology; D016193:G1 Phase / Q000187:drug effects; D006918:Hydroxyurea / Q000494:pharmacology; D051379:Mice; D008898:Mimosine / Q000494:pharmacology; D051135:Rad51 Recombinase; D011995:Recombination, Genetic; D016196:S Phase / Q000187:drug effects
D004268:DNA-Binding Proteins; D016590:Aphidicolin; D008898:Mimosine; D051135:Rad51 Recombinase; C495154:Rad51 protein, mouse; D006918:Hydroxyurea