De novo deletions and duplications at recombination hotspots in mouse germlines.
Cell
; 184(24): 5970-5984.e18, 2021 11 24.
Article
in En
| MEDLINE
| ID: mdl-34793701
ABSTRACT
Numerous DNA double-strand breaks (DSBs) arise during meiosis to initiate homologous recombination. These DSBs are usually repaired faithfully, but here, we uncover a distinct type of mutational event in which deletions form via joining of ends from two closely spaced DSBs (double cuts) within a single hotspot or at adjacent hotspots on the same or different chromatids. Deletions occur in normal meiosis but are much more frequent when DSB formation is dysregulated in the absence of the ATM kinase. Events between chromosome homologs point to multi-chromatid damage and aborted gap repair. Some deletions contain DNA from other hotspots, indicating that double cutting at distant sites creates substrates for insertional mutagenesis. End joining at double cuts can also yield tandem duplications or extrachromosomal circles. Our findings highlight the importance of DSB regulation and reveal a previously hidden potential for meiotic mutagenesis that is likely to affect human health and genome evolution.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Recombination, Genetic
/
Gene Deletion
/
Gene Duplication
/
Germ Cells
Limits:
Animals
Language:
En
Journal:
Cell
Year:
2021
Document type:
Article
Affiliation country:
United States