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Gene duplication and deletion caused by over-replication at a fork barrier

Abstract:
Replication fork stalling can provoke fork reversal to form a four-way DNA junction. This remodelling of the replication fork can facilitate repair, aid bypass of DNA lesions, and enable replication restart, but may also pose a risk of over-replication during fork convergence. We show that replication fork stalling at a site-specific barrier in fission yeast can induce gene duplication-deletion rearrangements that are independent of replication restart-associated template switching and Rad51-dependent multi-invasion. Instead, they resemble targeted gene replacements (TGRs), requiring the DNA annealing activity of Rad52, the 3'-flap nuclease Rad16-Swi10, and mismatch repair protein Msh2. We propose that excess DNA, generated during the merging of a canonical fork with a reversed fork, can be liberated by a nuclease and integrated at an ectopic site via a TGR-like mechanism. This highlights how over-replication at replication termination sites can threaten genome stability in eukaryotes.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41467-023-43494-7

Authors

More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Biochemistry
Role:
Author
ORCID:
0000-0002-8397-6492
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Biochemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Biochemistry
Role:
Author


Publisher:
Springer Nature
Journal:
Nature Communications More from this journal
Volume:
14
Issue:
1
Article number:
7730
Publication date:
2023-11-25
Acceptance date:
2023-11-10
DOI:
EISSN:
2041-1723


Language:
English
Keywords:
Pubs id:
1570014
Local pid:
pubs:1570014
Deposit date:
2023-11-24
ARK identifier:

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