Loss of Werner syndrome protein function promotes aberrant mitotic recombination.
The chromosome 8p11-12 Werner syndrome (WRN ) locus encodes a RecQ helicase protein of unknown function that possesses both 3' --> 5' helicase and 3' --> 5' exonuclease activities. We show that WRN cell lines display a marked reduction in cell proliferation following mitotic recombination, and generate few viable gene conversion-type recombinants. These findings indicate that WRN plays a role in mitotic recombination, and that a loss of WRN function may promote genetic instability and disease via recombination-initiated mitotic arrest, cell death, or gene rearrangement.
Prince
P R
PR
University of Washington, Department of Pathology, Seattle, Washington 98195-7705, USA.
Emond
M J
MJ
Monnat
R J
RJ
D016923:Cell Death; D002455:Cell Division; D002460:Cell Line; D002898:Chromosomes, Human, Pair 8; D004265:DNA Helicases / Q000235:genetics* / Q000502:physiology*; D005090:Exodeoxyribonucleases; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008938:Mitosis; D008954:Models, Biological; D008957:Models, Genetic; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D053484:RecQ Helicases; D011995:Recombination, Genetic; D014898:Werner Syndrome / Q000235:genetics*; D000071657:Werner Syndrome Helicase
D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase