Homology-directed repair of DNA nicks via pathways distinct from canonical double-strand break repair
Abstract
Nicks are a very common form of DNA damage, but their threat to genomic integrity has been neglected because it is assumed that all nicks are repaired by simple religation. Here we challenge that assumption. We identify a robust pathway for homology-directed repair (HDR) that is active at DNA nicks. This alternative HDR pathway is stimulated upon down-regulation of key factors in canonical HDR at double-strand breaks. Alternative HDR at targeted nicks has immediate practical applications to genome engineering. Alternative HDR can promote repair of a nicked target by a nicked donor and may thereby contribute to loss of heterozygosity, a common form of genomic instability in tumors.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- March 2014
- DOI:
- 10.1073/pnas.1400236111
- Bibcode:
- 2014PNAS..111E.924D