Dna2 nuclease deficiency results in large and complex DNA insertions at chromosomal breaks.

ABSTRACT: Insertions of mobile elements^1-4, mitochondrial DNA⁵ and fragments of nuclear chromosomes⁶ at DNA double-strand breaks (DSBs) threaten genome integrity and are common in cancer^7-9. Insertions of chromosome fragments at V(D)J recombination loci can stimulate antibody diversification¹⁰. The origin of insertions of chromosomal fragments and the mechanisms that prevent such insertions remain unknown. Here we reveal a yeast mutant, lacking evolutionarily conserved Dna2 nuclease, that shows frequent insertions of sequences between approximately 0.1 and 1.5 kb in length into DSBs, with many insertions involving multiple joined DNA fragments. Sequencing of around 500 DNA inserts reveals that they originate from Ty retrotransposons (8%), riboso

SUBMITTER: Yu Y 

PROVIDER: S-EPMC6346745 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature