title: Genomic rearrangements induced by unscheduled DNA double strand breaks in somatic mammalian cells.
abstract: DNA double-strand breaks (DSBs) are highly toxic lesions that can lead to profound genome rearrangements and/or cell death. They routinely occur in genomes due to endogenous or exogenous stresses. Efficient repair systems, canonical non-homologous end-joining and homologous recombination exist in the cell and not only ensure the maintenance of genome integrity but also, via specific programmed DNA double-strand breaks, permit its diversity and plasticity. However, these repair systems need to be tightly controlled because they can also generate genomic rearrangements. Thus, when DSB repair is not properly regulated, genome integrity is no longer guaranteed. In this review, we will focus on non-programmed genome rearrangements generated by DSB repair, in somatic cells. We first discuss genome rearrangements induced by homologous recombination and end-joining. We then discuss recently described rearrangement mechanisms, driven by microhomologies, that do not involve the joining of DNA ends but rather initiate DNA synthesis (microhomology-mediated break-induced replication, fork stalling and template switching and microhomology-mediated template switching). Finally, we discuss chromothripsis, which is the shattering of a localized region of the genome followed by erratic rejoining.
authors.affiliation: CNRS UMR 8200, Institut de Cancérologie Gustave-Roussy, Université Paris-Saclay, Equipe Labellisée Ligue Contre le Cancer, Villejuif, France.
authors.forename: Ayeong
authors.initials: A
authors.lastname: So
authors.affiliation: CNRS UMR 8200, Institut de Cancérologie Gustave-Roussy, Université Paris-Saclay, Equipe Labellisée Ligue Contre le Cancer, Villejuif, France.
authors.forename: Tangui
authors.initials: T
authors.lastname: Le Guen
authors.affiliation: CNRS UMR 8200, Institut de Cancérologie Gustave-Roussy, Université Paris-Saclay, Equipe Labellisée Ligue Contre le Cancer, Villejuif, France.
authors.forename: Bernard S
authors.initials: BS
authors.lastname: Lopez
authors.affiliation: CNRS UMR 8200, Institut de Cancérologie Gustave-Roussy, Université Paris-Saclay, Equipe Labellisée Ligue Contre le Cancer, Villejuif, France.
authors.forename: Josée
authors.initials: J
authors.lastname: Guirouilh-Barbat
mesh_terms: D000818:Animals; D000072837:Chromothripsis; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D004260:DNA Repair; D015321:Gene Rearrangement; D042822:Genomic Instability; D006801:Humans; D008957:Models, Genetic; D018384:Oxidative Stress; D059767:Recombinational DNA Repair; D013312:Stress, Physiological; D015854:Up-Regulation
keywords: double strand break; double strand break repair; genome instability; genome rearrangements; homologous recombination; non-homologous end-joining