title: DNA damage tolerance by recombination: Molecular pathways and DNA structures.
abstract: Replication perturbations activate DNA damage tolerance (DDT) pathways, which are crucial to promote replication completion and to prevent fork breakage, a leading cause of genome instability. One mode of DDT uses translesion synthesis polymerases, which however can also introduce mutations. The other DDT mode involves recombination-mediated mechanisms, which are generally accurate. DDT occurs prevalently postreplicatively, but in certain situations homologous recombination is needed to restart forks. Fork reversal can function to stabilize stalled forks, but may also promote error-prone outcome when used for fork restart. Recent years have witnessed important advances in our understanding of the mechanisms and DNA structures that mediate recombination-mediated damage-bypass and highlighted principles that regulate DDT pathway choice locally and temporally. In this review we summarize the current knowledge and paradoxes on recombination-mediated DDT pathways and their workings, discuss how the intermediate DNA structures may influence genome integrity, and outline key open questions for future research.
authors.affiliation: IFOM, The FIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy. Electronic address: dana.branzei@ifom.eu.
authors.forename: Dana
authors.initials: D
authors.lastname: Branzei
authors.affiliation: IFOM, The FIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy.
authors.forename: Barnabas
authors.initials: B
authors.lastname: Szakal
mesh_terms: D000818:Animals; D020137:Base Pair Mismatch; D004247:DNA / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D053843:DNA Mismatch Repair; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D042822:Genomic Instability; D006801:Humans; D008322:Mammals; D059767:Recombinational DNA Repair; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; D004259:DNA-Directed DNA Polymerase; D004265:DNA Helicases
keywords: Chromosome replication; DNA damage tolerance; Fork reversal; Homologous recombination; PCNA; Replication stress; Ubiquitin/SUMO modifications