Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 149-156 |
| Number of pages | 8 |
| Journal | Oncogene |
| Volume | 23 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 8 2004 |
Bibliographical note
Funding Information:We thank Titia de Lange for providing constructs for overproduction of TRF1 and TRF2 and for helpful comments. This work was supported in part by Grant NS-008900 from the Ellison Medical Foundation to DKO.
Funding
We thank Titia de Lange for providing constructs for overproduction of TRF1 and TRF2 and for helpful comments. This work was supported in part by Grant NS-008900 from the Ellison Medical Foundation to DKO.
| Funders | Funder number |
|---|---|
| Ellison Medical Foundation |
Keywords
- Aging
- Cancer
- Cellular senescence
- RecQ helicases
- Telomeres
- Werner syndrome
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research
