In eukaryotes, homologous recombination (HR) provides an important means to eliminate
DNA double-stranded breaks and other chromosomal lesions. Accordingly, failure in HR leads to
genomic instability and a predisposition to various
cancer types. While HR is clearly beneficial for genome maintenance, inappropriate or untimely events can be harmful. For this reason, HR must be tightly regulated. Several
DNA helicases contribute to HR regulation, by way of mechanisms that are conserved from yeast to humans. Mutations in several HR-specific helicases e.g. BLM and RECQ5, are either associated with
cancer-prone human syndromes or engender the
cancer phenotype in animal models. Therefore, delineating the role of
DNA helicases in HR regulation has direct relevance to
cancer etiology. Genetic, cytological, biochemical, and other analyses have shown that
DNA helicases participate in early or late stages of HR, to disrupt
nucleoprotein filaments that harbor the
Rad51 recombinase or dissociate the D-loop intermediate made by Rad51, or to prevent undesirable events and/or minimize potentially deleterious crossover products. Moreover, the ensemble that harbors BLM and
topoisomerase IIIalpha can dissolve the double-
Holliday junction, a complex
DNA intermediate generated during HR, to produce non-crossover products. These regulatory pathways function in parallel to promote the usage of the genome-preserving synthesis-dependent strand annealing HR pathway or otherwise suppress crossover formation.