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

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  • Judith Oehler

    (University of Oxford)

  • Carl A. Morrow

    (University of Oxford)

  • Matthew C. Whitby

    (University of Oxford)

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.

Suggested Citation

  • Judith Oehler & Carl A. Morrow & Matthew C. Whitby, 2023. "Gene duplication and deletion caused by over-replication at a fork barrier," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43494-7
    DOI: 10.1038/s41467-023-43494-7
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    References listed on IDEAS

    as
    1. Karel Naiman & Eduard Campillo-Funollet & Adam T. Watson & Alice Budden & Izumi Miyabe & Antony M. Carr, 2021. "Replication dynamics of recombination-dependent replication forks," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    2. Anastasiya Kishkevich & Sanjeeta Tamang & Michael O. Nguyen & Judith Oehler & Elena Bulmaga & Christos Andreadis & Carl A. Morrow & Manisha Jalan & Fekret Osman & Matthew C. Whitby, 2022. "Rad52’s DNA annealing activity drives template switching associated with restarted DNA replication," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Yilong Li & Nicola D. Roberts & Jeremiah A. Wala & Ofer Shapira & Steven E. Schumacher & Kiran Kumar & Ekta Khurana & Sebastian Waszak & Jan O. Korbel & James E. Haber & Marcin Imielinski & Joachim We, 2020. "Patterns of somatic structural variation in human cancer genomes," Nature, Nature, vol. 578(7793), pages 112-121, February.
    4. Karol Kramarz & Kamila Schirmeisen & Virginie Boucherit & Anissia Ait Saada & Claire Lovo & Benoit Palancade & Catherine Freudenreich & Sarah A. E. Lambert, 2020. "The nuclear pore primes recombination-dependent DNA synthesis at arrested forks by promoting SUMO removal," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    5. Roxanne Oshidari & Richard Huang & Maryam Medghalchi & Elizabeth Y. W. Tse & Nasser Ashgriz & Hyun O. Lee & Haley Wyatt & Karim Mekhail, 2020. "DNA repair by Rad52 liquid droplets," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
    6. Christian J. Rudolph & Amy L. Upton & Anna Stockum & Conrad A. Nieduszynski & Robert G. Lloyd, 2013. "Avoiding chromosome pathology when replication forks collide," Nature, Nature, vol. 500(7464), pages 608-611, August.
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