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

Lambert, S., Watson, A., Sheedy, D. M., Martin, B. and Carr, A. M. (2005) Gross chromosomal rearrangements and elevated recombination at an inducible site-specific replication fork barrier. Cell, 121 (5). pp. 689-702. ISSN 0092-8674

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Abstract

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.

Item Type: Article
Additional Information: 0092-8674 Journal Article GDSC139
Schools and Departments: School of Life Sciences
Depositing User: Gee Wheatley
Date Deposited: 19 Mar 2007
Last Modified: 30 Nov 2012 16:51
URI: http://sro.sussex.ac.uk/id/eprint/941
Google Scholar:109 Citations
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