Basic domain of telomere guardian TRF2 reduces D-loop unwinding whereas Rap1 restores it

NEČASOVÁ, Ivona, Eliška JANOUŠKOVÁ, Tomáš KLUMPLER and Ctirad HOFR. Basic domain of telomere guardian TRF2 reduces D-loop unwinding whereas Rap1 restores it. Nucleic Acids Research. 2017, vol. 45, No 21, p. 12170-12180. ISSN 0305-1048. Available from: https://dx.doi.org/10.1093/nar/gkx812.

Basic information

Original name

Basic domain of telomere guardian TRF2 reduces D-loop unwinding whereas Rap1 restores it

Authors

NEČASOVÁ, Ivona (203 Czech Republic, belonging to the institution), Eliška JANOUŠKOVÁ (203 Czech Republic, belonging to the institution), Tomáš KLUMPLER (203 Czech Republic, belonging to the institution) and Ctirad HOFR (203 Czech Republic, guarantor, belonging to the institution)

Edition

Nucleic Acids Research, 2017, 0305-1048

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Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10610 Biophysics

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

LifeB - Laboratory of interaction and function of essential biomolecules Basic domain of telomere guardian TRF2 reduces D-loop unwinding whereas Rap1 restores it

Impact factor

Impact factor: 11.561

RIV identification code

RIV/00216224:14740/17:00095119

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1093/nar/gkx812

UT WoS

000417691300016

Keywords in English

TRF2; DNA; telomere; D-loop; Rap1

Tags

MEDGENET, OA, rivok

Tags

International impact, Reviewed

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Abstract

V originále

Telomeric repeat binding factor 2 (TRF2) folds human telomeres into loops to prevent unwanted DNA repair and chromosome end-joining. The N-terminal basic domain of TRF2 (B-domain) protects the telomeric displacement loop (D-loop) from cleavage by endonucleases. Repressor activator protein 1 (Rap1) binds TRF2 and improves telomeric DNA recognition. We found that the B-domain of TRF2 stabilized the D-loop and thus reduced unwinding by BLM and RPA, whereas the formation of the Rap1–TRF2 complex restored DNA unwinding. To understand how the B-domain of TRF2 affects DNA binding and D-loop processing, we analyzed DNA binding of full-length TRF2 and a truncated TRF2 construct lacking the B-domain. We quantified how the B-domain improves TRF2’s interaction with DNA via enhanced long-range electrostatic interactions. We developed a structural envelope model of the B-domain bound on DNA. The model revealed that the B-domain is flexible in solution but becomes rigid upon binding to telomeric DNA. We proposed a mechanism for how the B-domain stabilizes the D-loop.

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Links

GA16-20255S, research and development project	Name: Molekulární mechanismus inhibice telomerázy: cílené zastavení dělení nádorových buněk Investor: Czech Science Foundation
LQ1601, research and development project	Name: CEITEC 2020 (Acronym: CEITEC2020) Investor: Ministry of Education, Youth and Sports of the CR
692298, interní kód MU	Name: MEDGENET - Medical genomics and epigenomics network (Acronym: MEDGENET) Investor: European Union, Spreading excellence and widening participation