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Genomic rearrangements induced by unscheduled DNA double strand breaks in somatic mammalian cells
Author(s) -
So Ayeong,
Le Guen Tangui,
Lopez Bernard S.,
GuirouilhBarbat Josée
Publication year - 2017
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14053
Subject(s) - homologous recombination , chromothripsis , biology , genome , genome instability , genetics , dna repair , dna , homology directed repair , non homologous end joining , somatic cell , computational biology , dna damage , gene , dna mismatch repair
DNA double‐strand breaks ( DSB s) 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.