Lack of WRN results in extensive deletion at nonhomologous joining ends.
Loss of WRN causes the genomic instability progeroid syndrome, Werner syndrome. WRN encodes a multifunctional nuclear protein with 3'-->5' exonuclease and 3'-->5' helicase activities. Linear plasmids with noncompatible ends introduced to Werner syndrome cells underwent extensive deletions at nonhomologous joining ends, particularly at the 3' protruding single-stranded end. This extensive deletion phenotype was complemented by wild-type WRN. These results suggest that WRN can out-compete other exonucleases that participate in double-strand break repair or stabilize the broken DNA end.
Oshima
Junko
J
Department of Pathology, University of Washington, Seattle, Washington, 98195, USA.
Huang
Shurong
S
Pae
Chong
C
Campisi
Judith
J
Schiestl
Robert H
RH
D004247:DNA / Q000235:genetics* / Q000378:metabolism; D004265:DNA Helicases / Q000235:genetics*; D004260:DNA Repair; D005090:Exodeoxyribonucleases; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D017353:Gene Deletion; D006801:Humans; D008297:Male; D010957:Plasmids / Q000235:genetics; D053484:RecQ Helicases; D014162:Transfection; D014898:Werner Syndrome / Q000235:genetics* / Q000473:pathology; D000071657:Werner Syndrome Helicase
D004247:DNA; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase