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Homologous recombination and the formation of complex genomic rearrangements

Aurèle Piazza and Wolf-Dietrich Heyer (2019)

Trends in cell biology, 29(2):135–149.

The maintenance of genome integrity involves multiple independent DNA damage avoidance and repair mechanisms. Yet, the origin and pathways of the focal chromosomal reshuffling phenomena collectively referred to as chromothripsis remain mechanistically obscure. Here ,we discuss the role, mechanisms, and regulation of HR in the formation of simple and complex chromosomal rearrangements. We emphasize features of the recently characterized Multi-invasions Induced Rearrangement (MIR) pathway, which uniquely amplifies the initial DNA damage. HR intermediates and cellular contexts at risk for genomic stability are discussed along with the emerging roles of various classes of nucleases in the formation of genome rearrangements. Long-read sequencing and improved mapping of repeats should enable better appreciation of the significance of recombination in generating genomic rearrangements.