Investigation of replication initiation inhibitory activity in the Mcm4 N-terminus

Diplôme Master Investigation of replication initiation inhibitory activity in the Mcm4 N-terminus eng 2019 author Ivanitsa Vitalii 875423 director Shore David M. 102587 DNA replication initiation is a first step of genomic duplication. During initiation the ‘replisome' is assembled. Its core and engine, the CMG (Cdc45, MCM, GINs) helicase, is loaded onto the origins and activated. These events are promoted by the activity of DDK and S-CDK kinases. Previously, our lab identified new Mcm4 point mutants capable of supporting CMG helicase assembly in cells with dramatically reduced DDK activity through a suppressor screen. In this work, we tried to elucidate the exact region of Mcm4-NSD (N- terminal Serine/Threonine rich domain) responsible for inhibiting replication initiation and the molecular mechanism underlying the process. We found a conserved motif located between amino acids (aa) 134-138 of Mcm4-NSD. The elimination of this motif rescued cells in cdc7-4 ts or cdc7Δ backgrounds. The phenotype of mutants assessed by growth or spore viability assays confirmed the intrinsic inhibitory function within the proximal subdomain (aa 74-174) of Mcm4. DNA replication Replication initiation Mcm Bob2 Helicase Helicase activation Dewey 570 43 Département de biologie moléculaire 161 false 813 Groupe Shore 7ceb2245-e6a7-4ebf-a5c2-36b227811c34 Master thesis Restricted Vitalii_Ivanitsa_MSc_thesis.pdf 3608185 application/pdf Private 2020-12-04 restrictedAccess Faculté des sciences / Section de biologie / Département de biologie moléculaire

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Investigation of replication initiation inhibitory activity in the Mcm4 N-terminus				2019	90	0

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Ivanitsa, Vitalii