Abstract |
Most cancer cells activate telomerase to elongate telomeres and achieve unlimited replicative potential. Some cancer cells cannot activate telomerase and use telomere homologous recombination (HR) to elongate telomeres, a mechanism termed alternative lengthening of telomeres (ALT). A hallmark of ALT cells is the recruitment of telomeres to PML bodies (termed APBs). Here, we show that the SMC5/6 complex localizes to APBs in ALT cells and is required for targeting telomeres to APBs. The MMS21 SUMO ligase of the SMC5/6 complex SUMOylates multiple telomere-binding proteins, including TRF1 and TRF2. Inhibition of TRF1 or TRF2 SUMOylation prevents APB formation. Depletion of SMC5/6 subunits by RNA interference inhibits telomere HR, causing telomere shortening and senescence in ALT cells. Thus, the SMC5/6 complex facilitates telomere HR and elongation in ALT cells by promoting APB formation through SUMOylation of telomere-binding proteins.
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Authors | Patrick Ryan Potts, Hongtao Yu |
Journal | Nature structural & molecular biology
(Nat Struct Mol Biol)
Vol. 14
Issue 7
Pg. 581-90
(Jul 2007)
ISSN: 1545-9993 [Print] United States |
PMID | 17589526
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cell Cycle Proteins
- Chromosomal Proteins, Non-Histone
- SMC5 protein, human
- SMC6 protein, human
- Small Ubiquitin-Related Modifier Proteins
- Telomeric Repeat Binding Protein 1
- Telomeric Repeat Binding Protein 2
- Ligases
- NSMCE2 protein, human
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Topics |
- Cell Cycle Proteins
(analysis, antagonists & inhibitors, metabolism)
- Cell Line, Tumor
- Chromosomal Proteins, Non-Histone
- Humans
- Ligases
(metabolism)
- Neoplasms
(genetics)
- Protein Processing, Post-Translational
- Recombination, Genetic
- Small Ubiquitin-Related Modifier Proteins
(metabolism)
- Telomere
(chemistry, genetics)
- Telomeric Repeat Binding Protein 1
(metabolism)
- Telomeric Repeat Binding Protein 2
(metabolism)
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