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Gross chromosomal rearrangements and elevated recombination at an inducible site-specific replication fork barrier

journal contribution
posted on 2023-06-07, 13:53 authored by S. Lambert, Adam WatsonAdam Watson, D. M. Sheedy, B. Martin, Antony CarrAntony Carr
Genomic rearrangements linked to aberrant recombination are associated with cancer and human genetic diseases. Such recombination has indirectly been linked to replication fork stalling. Using fission yeast, we have developed a genetic system to block replication forks at nonhistone/DNA complexes located at a specific euchromatic site. We demonstrate that stalled replication forks lead to elevated intrachromosomal and ectopic recombination promoting site-specific gross chromosomal rearrangements. We show that recombination is required to promote cell viability when forks are stalled, that recombination proteins associate with sites of fork stalling, and that recombination participates in deleterious site-specific chromosomal rearrangements. Thus, recombination is a "double-edged sword," preventing cell death when the replisome disassembles at the expense of genetic stability.

History

Publication status

  • Published

Journal

Cell

ISSN

0092-8674

Issue

5

Volume

121

Page range

689-702

Notes

GDSC139

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2007-03-19

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