کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5527189 1401569 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The human CTC1/STN1/TEN1 complex regulates telomere maintenance in ALT cancer cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
The human CTC1/STN1/TEN1 complex regulates telomere maintenance in ALT cancer cells
چکیده انگلیسی


- CST localizes at telomeres and ALT-associated PML bodies in ALT cells throughout the cell cycle.
- CST is important for promoting telomeric DNA replication in ALT cells.
- CST deficiency decreases ECTR formation and increases T-SCE.
- CST deficiency impairs ALT cell proliferation and results in multinucleation.

Maintaining functional telomeres is important for long-term proliferation of cells. About 15% of cancer cells are telomerase-negative and activate the alternative-lengthening of telomeres (ALT) pathway to maintain their telomeres. Recent studies have shown that the human CTC1/STN1/TEN1 complex (CST) plays a multi-faceted role in telomere maintenance in telomerase-expressing cancer cells. However, the role of CST in telomere maintenance in ALT cells is unclear. Here, we report that human CST forms a functional complex localizing in the ALT-associated PML bodies (APBs) in ALT cells throughout the cell cycle. Suppression of CST induces telomere instabilities including telomere fragility and elevates telomeric DNA recombination, leading to telomere dysfunction. In addition, CST deficiency significantly diminishes the abundance of extrachromosomal circular telomere DNA known as C-circles and t-circles. Suppression of CST also results in multinucleation in ALT cells and impairs cell proliferation. Our findings imply that the CST complex plays an important role in regulating telomere maintenance in ALT cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 355, Issue 2, 15 June 2017, Pages 95-104
نویسندگان
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