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Science Forum Index » Life Extension Forum » telomeres, aging and werner syndrome
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| rs |
 Posted: Fri Jan 09, 2004 3:44 pm |
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Oncogene. 2004 Jan 8;23(1):149-56.
TRF2 recruits the Werner syndrome (WRN) exonuclease for processing of
telomeric DNA.
Machwe A, Xiao L, Orren DK.
1Graduate Center for Toxicology, University of Kentucky, Lexington, KY
40536-0305, USA.
The cancer-prone and premature aging disease Werner syndrome is due to
loss of WRN gene function. Cells lacking WRN demonstrate genomic
instability, including telomeric abnormalities and undergo premature
senescence, suggesting defects in telomere metabolism. This notion is
strongly supported by our finding of physical and functional
interactions between WRN and TRF2, a telomeric repeat binding factor
essential for proper telomeric structure. TRF2 binds to DNA substrates
containing telomeric repeats and facilitates their degradation
specifically by WRN exonuclease activity. WRN and TRF2 also interact
directly in the absence of DNA. These results suggest that TRF2
recruits WRN for accurate processing of telomeric structures in vivo.
Thus, our findings link problems in telomere maintenance to both
carcinogenesis and specific features of aging.Oncogene (2004) 23,
149-156. doi:10.1038/sj.onc.1206906
PMID: 14712220 [PubMed - in process] |
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