Rescue of arrested replication forks by homologous recombination

DNA synthesis is an accurate and very processive phenomenon; nevertheless, replication fork progression on chromosomes can be impeded by DNA lesions, DNA secondary structures, or DNA-bound proteins. Elements interfering with the progression of replication forks have been reported to induce rearrange ments and/or render homologous recombination essential for viability, in al l organisms from bacteria to human. Arrested replication forks may be the t arget of nucleases, thereby providing a substrate for double-strand break r epair enzyme. For example in bacteria, direct fork breakage was proposed to occur at replication forks blocked by a bona fide replication terminator s equence, a specific site that arrests bacterial chromosome replication. Alt ernatively, an arrested replication fork may be transformed into a recombin ation substrate by reversal of the forked structures. In reversed forks, th e last duplicated portions of the template strands reanneal, allowing the n ewly synthesized strands to pair. In bacteria, this reaction was proposed t o occur in replication mutants, in which fork arrest is caused by a defect in a replication protein, and in UV irradiated cells. Recent studies sugges t that it may also occur in eukaryote organisms. We will review here observ ations that link replication hindrance with DNA rearrangements and the poss ible underlying molecular processes.