Article abstract
Nature Structural & Molecular Biology 14, 581 - 590 (2007)
Published online: 24 June 2007 | doi:10.1038/nsmb1259
The SMC5/6 complex maintains telomere length in ALT cancer cells through SUMOylation of telomere-binding proteins
Patrick Ryan Potts1 & Hongtao Yu1
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.
- Department of Pharmacology, The University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, Texas 75390-9041, USA.
Correspondence to: Hongtao Yu1 e-mail: hongtao.yu@utsouthwestern.edu
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