BACKGROUND: Werner syndrome (WS) results from defects in the RecQ helicase (WRN) 
and is characterized by premature aging and accelerated tumorigenesis. 
Contradictorily, WRN deficient human fibroblasts derived from WS patients show a 
characteristically slower cell proliferation rate, as do primary fibroblasts and 
human cancer cell lines with WRN depletion. Previous studies reported that WRN 
silencing in combination with deficiency in other genes led to significantly 
accelerated cellular proliferation and tumorigenesis. The aim of the present 
study was to examine the effects of silencing WRN in p53 deficient HL60 and p53 
wild-type TK6 hematopoietic cells, in order to further the understanding of 
WRN-associated tumorigenesis.
METHODOLOGY/PRINCIPAL FINDINGS: We found that silencing WRN accelerated the 
proliferation of HL60 cells and decreased the cell growth rate of TK6 cells. 
Loss of WRN increased DNA damage in both cell types as measured by COMET assay, 
but elicited different responses in each cell line. In HL60 cells, but not in 
TK6 cells, the loss of WRN led to significant increases in levels of 
phosphorylated RB and numbers of cells progressing from G1 phase to S phase as 
shown by cell cycle analysis. Moreover, WRN depletion in HL60 cells led to the 
hyper-activation of homologous recombination repair via up-regulation of RAD51 
and BLM protein levels. This resulted in DNA damage disrepair, apparent by the 
increased frequencies of both spontaneous and chemically induced structural 
chromosomal aberrations and sister chromatid exchanges.
CONCLUSIONS/SIGNIFICANCE: Together, our data suggest that the effects of WRN 
silencing on cell proliferation and genomic instability are modulated probably 
by other genetic factors, including p53, which might play a role in the 
carcinogenesis induced by WRN deficiency.