Rad52's DNA annealing activity drives template switching associated with restarted DNA replication.

Autor: Kishkevich A; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK., Tamang S; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK., Nguyen MO; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK., Oehler J; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK., Bulmaga E; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK., Andreadis C; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK., Morrow CA; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK., Jalan M; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK., Osman F; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK., Whitby MC; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK. matthew.whitby@bioch.ox.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Nov 26; Vol. 13 (1), pp. 7293. Date of Electronic Publication: 2022 Nov 26.
DOI: 10.1038/s41467-022-35060-4
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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