Understanding Initiation of DNA Replication

Diplôme Thèse Understanding Initiation of DNA Replication eng 2022-06-17 2022-06-20 author Sosenko Anastasia 884290 director Halazonetis Thanos 641033 125 10.13097/archive-ouverte/unige:162442 urn:nbn:ch:unige-1624424 Sc. Vie 164 <p> The first step during the genome duplication is the initiation of DNA replication, i.e., the recognition of the DNA replication origins (ORIs) by the appropriate protein complexes, the loading of the DNA helicase (origin licensing) and the first DNA unwinding (origin firing). Towards a better comprehension of this process in human cells, we initially aimed to investigate the molecular mechanisms of ORI recognition, focusing on the aspect of sequence specificity. We found that a fraction of human ORIs contained a conserved motif, correspondent to the binding site for the AP-1 transcription factor and exhibited a reduced firing efficiency upon its deletion. In parallel, we studied the process of origin licensing and more precisely the period during the G1 phase when it occurs. We found that ORIs are licensed throughout the G1 phase, as licensing inhibition at any G1 timeframe impaired the entry into S phase and significantly reduced the origin firing efficiency. We are currently aiming to define whether different steps of origin licensing occur in early vs late G1 phase.</p> DNA replication ORI firing ORI licensing Motif Dewey 570 7daed2ee-1311-4824-9df9-2e51260a966a Département de biologie moléculaire et cellulaire 16484 false 811 Groupe Halazonetis 51c72046-1e36-4641-bacc-bbb8377442d4 Thesis Restricted Thesis_ASP_02-08-2022.pdf 21545619 application/pdf Private 2023-02-01 45612367c5c81553a5812b52e88886d08f29428b32dfabbbb1756b4d85e7beb5 ce00da0a-5fb7-4896-9c33-70286cd4084b Imprimatur Public Imprimatur.pdf 1661170 application/pdf adce8d0778f69100ad24677d264dfb86aa381e5bde5cc4a7f20595ef3db11667 restrictedAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire et cellulaire

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Understanding Initiation of DNA Replication				2022	487	31

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Sosenko, Anastasia

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