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Elucidating the molecular mechanism of cohesin-loading

Obiettivo

The cohesin-complex mediates sister chromatid cohesion from S-phase until mitosis and is involved in the formation of higher-order chromatin structure. To fulfill these vital functions, cohesin is loaded and positioned in the genome by mechanisms that are only poorly understood. In vitro, loading of cohesin on DNA only requires ATP and a loading-complex formed by Scc2-Scc4, while loading in vivo on chromatin is regulated by additional factors. For example, in Xenopus laevis oocytes, cohesin loading strictly depends on pre-replication complexes (pre-RCs), which are formed in telophase/G1.
Mechanistic studies are required to understand how cohesin-loading occurs at the molecular level. I will first determine the mechanism by which Scc2-Scc4 loads cohesin on DNA. Using single-molecule FRET and optical tweezers, I will monitor the effect of Scc2-Scc4 on conformational changes of cohesin as it is loaded on a DNA template. After characterizing this minimal loading reaction, I will reconstitute cohesin-loading during telophase/G1 using a purified system. With these experiments I will address why and how loading of cohesin is regulated by the formation of pre-RCs.

Campo scientifico (EuroSciVoc)

Parole chiave

Programma(i)

Argomento(i)

Meccanismo di finanziamento

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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(si apre in una nuova finestra) H2020-MSCA-IF-2015

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Coordinatore

FORSCHUNGSINSTITUT FUR MOLEKULARE PATHOLOGIE GESELLSCHAFT MBH
Contributo netto dell'UE
€ 166 156,80
Indirizzo
CAMPUS-VIENNA-BIOCENTER 1
1030 Wien
Austria
Regione
Ostösterreich Wien Wien
Tipo di attività
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Collegamenti
Costo totale
€ 166 156,80