Rad52’s DNA annealing activity drives template switching associated with restarted DNA replication
Anastasiya Kishkevich,
Sanjeeta Tamang,
Michael O. Nguyen,
Judith Oehler,
Elena Bulmaga,
Christos Andreadis,
Carl A. Morrow,
Manisha Jalan,
Fekret Osman and
Matthew C. Whitby ()
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Anastasiya Kishkevich: University of Oxford
Sanjeeta Tamang: University of Oxford
Michael O. Nguyen: University of Oxford
Judith Oehler: University of Oxford
Elena Bulmaga: University of Oxford
Christos Andreadis: University of Oxford
Carl A. Morrow: University of Oxford
Manisha Jalan: University of Oxford
Fekret Osman: University of Oxford
Matthew C. Whitby: University of Oxford
Nature Communications, 2022, vol. 13, issue 1, 1-13
Abstract:
Abstract It is thought that many of the simple and complex genomic rearrangements associated with congenital diseases and cancers stem from mistakes made during the restart of collapsed replication forks by recombination enzymes. It is hypothesised that this recombination-mediated restart process transitions from a relatively accurate initiation phase to a less accurate elongation phase characterised by extensive template switching between homologous, homeologous and microhomologous DNA sequences. Using an experimental system in fission yeast, where fork collapse is triggered by a site-specific replication barrier, we show that ectopic recombination, associated with the initiation of recombination-dependent replication (RDR), is driven mainly by the Rad51 recombinase, whereas template switching, during the elongation phase of RDR, relies more on DNA annealing by Rad52. This finding provides both evidence and a mechanistic basis for the transition hypothesis.
Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35060-4
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DOI: 10.1038/s41467-022-35060-4
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