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

Publikace nespadá pod Přírodovědeckou fakultu, ale pod Středoevropský technologický institut. Oficiální stránka publikace je na webu muni.cz.

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NEČASOVÁ Ivona JANOUŠKOVÁ Eliška KLUMPLER Tomáš HOFR Ctirad

Druh Článek v odborném periodiku
Časopis / Zdroj Nucleic Acids Research
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
WWW
Doi http://dx.doi.org/10.1093/nar/gkx812
Obor Biofyzika
Klíčová slova TRF2; DNA; telomere; D-loop; Rap1
Popis 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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