title: Nick-initiated homologous recombination: Protecting the genome, one strand at a time.
abstract: Homologous recombination (HR) is an essential, widely conserved mechanism that utilizes a template for accurate repair of DNA breaks. Some early HR models, developed over five decades ago, anticipated single-strand breaks (nicks) as initiating lesions. Subsequent studies favored a more double-strand break (DSB)-centered view of HR initiation and at present this pathway is primarily considered to be associated with DSB repair. However, mounting evidence suggests that nicks can indeed initiate HR directly, without first being converted to DSBs. Moreover, recent studies reported on novel branches of nick-initiated HR (nickHR) that rely on single-, rather than double-stranded repair templates and that are characterized by mechanistically and genetically unique properties. The physiological significance ofnickHR is not well documented, but its high-fidelity nature and low mutagenic potential are relevant in recently developed, precise gene editing approaches. Here, we review the evidence for stimulation of HR by nicks, as well as the data on the interactions ofnickHR with other DNA repair pathways and on its mechanistic properties. We conclude thatnickHR is a bona-fide pathway for nick repair, sharing the molecular machinery with the canonical HR but nevertheless characterized by unique properties that secure its inclusion in DNA repair models and warrant future investigations.
authors.affiliation: Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Lianne E M
authors.initials: LE
authors.lastname: Vriend
authors.affiliation: Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. Electronic address: p.krawczyk@amc.uva.nl.
authors.forename: Przemek M
authors.initials: PM
authors.lastname: Krawczyk
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism; D053960:DNA Breaks; D059766:DNA End-Joining Repair; D056890:Eukaryota / Q000235:genetics / Q000378:metabolism; D006801:Humans; D059767:Recombinational DNA Repair
chemical_list: D004247:DNA