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Identification and characterization of a Drosophila ortholog of WRN exonuclease that is required to maintain genome integrity

Saunders, R. D. C. and Boubriak, I. and Clancy, D. J. and Cox, L. S. (2008) Identification and characterization of a Drosophila ortholog of WRN exonuclease that is required to maintain genome integrity. Aging cell, 7 (3). pp. 418-425. ISSN 1474-9726

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Abstract

The premature human aging Werner syndrome (WS) is caused by mutation of the RecQ-family WRN helicase, which is unique in possessing also 3'-5' exonuclease activity. WS patients show significant genomic instability with elevated cancer incidence. WRN is implicated in restraining illegitimate recombination, especially during DNA replication. Here we identify a Drosophila ortholog of the WRN exonuclease encoded by the CG7670 locus. The predicted DmWRNexo protein shows conservation of structural motifs and key catalytic residues with human WRN exonuclease, but entirely lacks a helicase domain. Insertion of a piggyBac element into the 5' UTR of CG7670 severely reduces gene expression. DmWRNexo mutant flies homozygous for this insertional allele of CG7670 are thus severely hypomorphic; although adults show no gross morphological abnormalities, females are sterile. Like human WS cells, we show that the DmWRNexo mutant flies are hypersensitive to the topoisomerase I inhibitor camptothecin. Furthermore, these mutant flies show highly elevated rates of mitotic DNA recombination resulting from excessive reciprocal exchange. This study identifies a novel WRN ortholog in flies and demonstrates an important role for WRN exonuclease in maintaining genome stability.

Item Type: Article
Journal or Publication Title: Aging cell
Additional Information: Jun Identification and characterization of a Drosophila ortholog of WRN exonuclease that is required to maintain genome integrity Saunders, Robert D. C. Boubriak, Ivan Clancy, David J. Cox, Lynne S.
Uncontrolled Keywords: exonuclease ; Drosophila ; genome stability ; homologous recombination ; Werner syndrome ; WRN
Subjects: UNSPECIFIED
Departments: UNSPECIFIED
ID Code: 50151
Deposited By: ep_importer_pure
Deposited On: 30 Sep 2011 14:54
Refereed?: Yes
Published?: Published
Last Modified: 23 Jul 2014 14:55
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/50151

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