In all forms of life, genomic DNA is affected by chemical or physical damage that, if left unrepaired, could cause mutations. Single-strand DNA gaps count among these types of damage. They occur during the cell cycle's S phase, blocking the progression of the replication fork and that of the processive and accurate DNA polymerases. To prevent replication errors caused by them and avoid their accumulation behind the replication fork, the cycle comprises two pathways for overcoming these single-strand gaps. The first, called translesion synthesis, uses specialized DNA polymerases to place nucleotides in front of base lesions. This pathway suffers however from errors and may induce mutations. The second, called homologous recombination, uses the sister chromatid and/or a homologous chromosome as a template to fill the gap. To do so, this much more reliable pathway calls upon the recombinase Rad51, which assembles as filaments on the single-strand DNA. The balance between the error-prone and largely error-free pathways controls mutation levels. Precisely characterizing the factors influencing the choice of pathways is thus crucial for a better understanding of genetic stability at the replication fork. 

In a study performed in the yeast Saccharomyces cerevisiae and published in PLoS Genetics, researchers from the Laboratory of Genetic and Molecular Radiobiology teamed with their IRCM colleagues at the Telomeres and Chromosome Repair Laboratory and the Laboratory of Genome Instability and Nuclear Organization to study the role of the complex formed by the Rad51 paralog proteins Rad55 and Rad57 in the repair of single-strand DNA gaps and the balance between translesion synthesis and homologous recombination. In their work, the researchers submitted the yeast to either ultraviolet radiation, which mainly induces single-strand gaps, or gamma radiation, which also causes double-strand DNA breaks. They found that the Rad55-Rad57 complex was essential for the repair of single-strand gaps by homologous recombination in blocked DNA replication due to UV exposure, but not for the repair of double-strand breaks. The study's results also showed that the Rad51 filament stabilization conferred by the Rad55-Rad57 complex considerably reduced recruitment of translesional polymerases. Thus, that complex is a key factor in reducing mutagenesis associated with DNA replication.

This yeast study by the IRCM researchers suggests that inhibiting translesional polymerases may prove useful in malignancies, where cancer cells are deficient in Rad51 paralogs.