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The SMC5/6 complex maintains telomere length in ALT cancer cells through SUMOylation of telomere-binding proteins.

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.
AuthorsPatrick Ryan Potts, Hongtao Yu
JournalNature structural & molecular biology (Nat Struct Mol Biol) Vol. 14 Issue 7 Pg. 581-90 (Jul 2007) ISSN: 1545-9993 [Print] United States
PMID17589526 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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
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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