Chromothripsis refers to the catastrophic shattering of mis-segregated chromosomes, although the exact mechanism driving this process was unclear. Now, Engel et al. have identified the Fanconi anaemia (FA) pathway as a driver of chromothripsis.

Next, the authors found that in mitosis, following micronuclei formation, FA-deficient cells had reduced frequency of chromosome shattering compared to FA-proficient cells, suggesting that extensive chromosomal shattering requires the FA pathway. Through immunofluorescence, FANCD2, a component of the FA pathway found to be enriched in the CRISPR screen, localized to shattered mitotic chromosomes. When both alleles of FANCD2 were knocked out, levels of γ-H2AX, a surrogate marker of chromothripsis in mitotic cells, were decreased, suggesting FANCD2 is needed for chromosomal shattering.