Telomeric overhang length determines structural dynamics and accessibility to telomerase and ALT associated proteins

Hwang, Helen; Kreig, Alex; Calvert, Jacob; Lormand, Justin; Kwon, Yongho; Daley, James M.; Sung, Patrick; Opresko, Patricia L.; Myong, Sua

doi:10.1016/j.str.2014.03.013

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Telomeric overhang length determines structural dynamics and accessibility to telomerase and ALT associated proteins

Published Date:

May 15 2014

Publisher's site:

http://dx.doi.org/10.1016/j.str.2014.03.013

Source:

Structure. 2014; 22(6):842-853.

[PDF-1.44 MB]

Details:

Alternative Title:

Structure

Personal Author:

Hwang, Helen ; Kreig, Alex ; Calvert, Jacob ; Lormand, Justin ; Kwon, Yongho ; ... More ▼

Description:

The G-rich single-stranded DNA at the 3' end of human telomeres can self-fold into G-quaduplex (GQ). However, telomere lengthening by telomerase or the recombination-based alternative lengthening of telomere (ALT) mechanism requires protein loading on the overhang. Using single-molecule fluorescence spectroscopy, we discovered that lengthening the telomeric overhang also increased the rate of dynamic exchanges between structural conformations. Overhangs with five to seven TTAGGG repeats, compared with four repeats, showed much greater dynamics and accessibility to telomerase binding and activity and loading of the ALT-associated proteins RAD51, WRN, and BLM. Although the eight repeats are highly dynamic, they can fold into two GQs, which limited protein accessibility. In contrast, the telomere-specific protein POT1 is unique in that it binds independently of repeat number. Our results suggest that the telomeric overhang length and dynamics may contribute to the regulation of telomere extension via telomerase action and the ALT mechanism.

Subject:

[+]

Pubmed ID:

24836024

Pubmed Central ID:

PMC4067947

Document Type:

Journal Article

Funding:

343 NIH 1 DP2 GM105453 A/DP/NCCDPHP CDC HHS/United States ; DP2 GM105453/GM/NIGMS NIH HHS/United States ; ES0515052/ES/NIEHS NIH HHS/United States ; F30 CA174323/CA/NCI NIH HHS/United States ; R01 ES015052/ES/NIEHS NIH HHS/United States ; ... More ▼

Collection(s):

CDC Public Access

Main Document Checksum:

[+]

Supporting Files:

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