Homologous Recombination in Lesion Bypass

Synopsis

Living cells possess a variety of repair pathways to cope with DNA damage; however, many lesions can escape repair and potentially block DNA replication and other cellular processes. Fortunately, cells have evolved mechanisms that allow the bypass or tolerance of these lesions for subsequent DNA repair. In eukaryotes, lesion bypass occurs primarily via the Rad6-Rad18-dependent and homologous recombination (HR)-dependent pathways. The Rad6-Rad18 protein complex promotes lesion bypass by two main mechanisms: translesion synthesis (TLS) and template switching. Both TLS and template switching are regulated by posttranslational modifications of the DNA sliding clamp PCNA. TLS depends on specialized polymerases that can accommodate a variety of lesions within their active sites and thus replicate past damaged DNA. In budding yeast, TLS polymerases are recruited to damage sites by monoubiquitination of PCNA, which results in error-free or error-prone bypass depending on the lesion...