Human Rap1 modulates TRF2 attraction to telomeric DNA

Logo poskytovatele
Logo poskytovatele
Logo poskytovatele
Logo poskytovatele

Varování

Publikace nespadá pod Ekonomicko-správní fakultu, ale pod Středoevropský technologický institut. Oficiální stránka publikace je na webu muni.cz.
Autoři

JANOUŠKOVÁ Eliška NEČASOVÁ Ivona PAVLOUŠKOVÁ Jana ZIMMERMANN Michal HLUCHÝ Milan MARINI PALOMEQUE María Victoria NOVÁKOVÁ Monika HOFR Ctirad

Rok publikování 2015
Druh Článek v odborném periodiku
Časopis / Zdroj Nucleic Acids Research
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www http://nar.oxfordjournals.org/content/43/5/2691.full.pdf+html
Doi http://dx.doi.org/10.1093/nar/gkv097
Obor Biochemie
Klíčová slova MAMMALIAN TELOMERES; HOLLIDAY JUNCTIONS; PROTEIN; PROTECTION; SHELTERIN; BINDING; LOOP; END; ATM; RECRUITMENT
Přiložené soubory
Popis More than two decades of genetic research have identified and assigned main biological functions of shelterin proteins that safeguard telomeres. However, a molecular mechanism of how each protein subunit contributes to the protecting function of the whole shelterin complex remains elusive. Human Repressor activator protein 1 (Rap1) forms a multifunctional complex with Telomeric Repeat binding Factor 2 (TRF2). Rap1-TRF2 complex is a critical part of shelterin as it suppresses homology-directed repair in Ku 70/80 heterodimer absence. To understand how Rap1 affects key functions of TRF2, we investigated full-length Rap1 binding to TRF2 and Rap1-TRF2 complex interactions with double-stranded DNA by quantitative biochemical approaches. We observed that Rap1 reduces the overall DNA duplex binding affinity of TRF2 but increases the selectivity of TRF2 to telomeric DNA. Additionally, we observed that Rap1 induces a partial release of TRF2 from DNA duplex. The improved TRF2 selectivity to telomeric DNA is caused by less pronounced electrostatic attractions between TRF2 and DNA in Rap1 presence. Thus, Rap1 prompts more accurate and selective TRF2 recognition of telomeric DNA and TRF2 localization on single/double-strand DNA junctions. These quantitative functional studies contribute to the understanding of the selective recognition of telomeric DNA by the whole shelterin complex.
Související projekty:

Používáte starou verzi internetového prohlížeče. Doporučujeme aktualizovat Váš prohlížeč na nejnovější verzi.