Interactions of telomeric proteins with nucleic acids: sequence recognition on intact and oxidatively damaged telomeres - Publikacja - MOST Wiedzy

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Interactions of telomeric proteins with nucleic acids: sequence recognition on intact and oxidatively damaged telomeres

Abstrakt

Telomeres are complex nucleoprotein assemblies that play a vital role in the maintenance of functional ends of linear chromosomes. Telomeric DNA, composed of tandem repeats of the 5'-TTAGGG-3' motif, solves the so-called end replication problem: as chromosomes shorten with each cell division, no information is lost, and the telomere can be re-extended. In the cell, many protein factors regulate telomere length, nuclear positioning and conformation in response to cell cycle progression and the cell's proliferative status. Several proteins bind directly to single- or double-stranded telomeric DNA to assemble the main shelterin complex or play accessory roles. However, these interactions will be perturbed when the easily oxidized telomeric DNA is exposed to oxidative stress. In my doctoral work, I used Molecular Dynamics approaches to study the dynamics of protein-DNA complex formation at telomeres on the atomistic level, arriving at the most comprehensive thermodynamic, kinetic and mechanistic description of this process to date, including the first observation of spontaneous complex formation. I then investigated the impact of oxidative lesions on telomeric proteins, showing how base modifications disrupt sequence recognition on telomeric DNA. Finally, I used quantum chemical simulations to assess the feasibility of covalent protein-DNA cross-link formation on telomeres.

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Pełna treść

pobierz publikację
pobrano 109 razy
Wersja publikacji
Accepted albo Published Version
Licencja
Creative Commons: CC-BY-SA otwiera się w nowej karcie

Słowa kluczowe

Informacje szczegółowe

Kategoria:
Doktoraty, rozprawy habilitacyjne, nostryfikacje
Typ:
praca doktorska pracowników zatrudnionych w PG oraz studentów studium doktoranckiego
Język:
angielski
Rok wydania:
2019
Weryfikacja:
Politechnika Gdańska

wyświetlono 141 razy

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