Nucleostemin prevents telomere damage by promoting PML-IV recruitment to SUMOylated TRF1

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Nucleostemin prevents telomere damage by promoting PML-IV recruitment to SUMOylated TRF1

Continuously dividing cells must be protected from telomeric and nontelomeric DNA damage in order to maintain their proliferative potential. Here, we report a novel telomere-protecting mechanism regulated by nucleostemin (NS). NS depletion increased the number of telomere damage foci in both telomerase-active (TA(+)) and alternative lengthening of telomere (ALT) cells and decreased the percenta...

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Nucleostemin inhibits TRF1 dimerization and shortens its dynamic association with the telomere.

TRF1 is a key component of the telomere-capping complex and binds double-strand telomeric DNA as homodimers. So far, it is not clear whether TRF1 dimerization coincides with its telomere binding or is actively controlled before it binds the telomere, and in the latter case, how this event might affect its telomere association. We previously found that TRF1 dimerization and its telomere binding ...

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Cell-cycle-dependent Xenopus TRF1 recruitment to telomere chromatin regulated by Polo-like kinase.

Telomeres are regulated by a homeostatic mechanism that includes telomerase and telomeric repeat binding proteins, TRF1 and TRF2. Recently, it has been hypothesized that telomeres assume distinct configurations in a cell-cycle-dependent manner, although direct biochemical evidence is lacking. Here we demonstrated that Xenopus TRF1 (xTRF1) associates with telomere chromatin specifically in mitot...

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Nucleostemin delays cellular senescence and negatively regulates TRF1 protein stability.

Nucleostemin (NS) encodes a nucleolar GTP-binding protein highly enriched in the stem cells and cancer cells. To determine its biological activity in vivo, we generated NS loss- and gain-of-function mouse models. The embryogenesis of homozygous NS-null (NS(-/-)) mice was aborted before the blastula stage. Although the growth and fertility of heterozygous NS-null (NS(+/-)) mice appeared normal, ...

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PML body meets telomere

The unlimited proliferation potential of cancer cells requires the maintenance of their telomeres. This is frequently accomplished by reactivation of telomerase. However, in a significant fraction of tumors an alternative lengthening of telomeres (ALT) mechanism is active. The molecular mechanism of the ALT pathway remains elusive. In particular, the role of characteristic complexes of promyelo...

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ژورنال

عنوان ژورنال: Journal of Cell Biology

سال: 2012

ISSN: 1540-8140,0021-9525

DOI: 10.1083/jcb.201109038