Covalent interstrand cross-links (ICLs) in the genome must be repaired quickly to avoid disruption of DNA-based cellular processes and additional damage to the DNA. Vertebrates can repair ICLs during DNA replication in a process that involves Fanconi anemia (FA) proteins and is also thought to require homologous recombination between sister chromatids. Long et al. used a Xenopus egg-based cell‐free system to show that in replication‐coupled ICL repair, Rad51 is required for homologous recombination of the double-strand break in the incised sister chromatid. Rad51 is loaded onto stalled replication forks before double-strand break formation, likely functioning to initiate strand invasion as soon as the break occurs. The FA protein complex acts upstream of homologous recombination during interstrand cross-link repair and is not required for Rad51 recruitment to chromatin.
D. T. Long, M. Räschle, V. Joukov, J. C. Walter, Mechanism of RAD51-dependent DNA interstrand cross-link repair. Science 333, 84–87 (2011). [Abstract] [Full Text]
