Non-homologous end joining shapes the genomic rearrangement landscape of chromothripsis from mitotic errors.

ABSTRACT: Mitotic errors generate micronuclei entrapping mis-segregated chromosomes, which are susceptible to catastrophic fragmentation through chromothripsis. The reassembly of fragmented chromosomes by error-prone DNA double-strand break (DSB) repair generates diverse genomic rearrangements associated with human diseases. How specific repair pathways recognize and process these lesions remains poorly understood. Here we use CRISPR/Cas9 to systematically inactivate distinct DSB repair pathways and interrogate the rearrangement landscape of fragmented chromosomes. Deletion of canonical non-homologous end joining (NHEJ) components substantially reduces complex rearrangements and shifts the rearrangement landscape toward simple alterations without the characteristic patterns of chromothripsis. Follow

SUBMITTER: Hu Q 

PROVIDER: S-EPMC11224358 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature