Control of chromosome duplication: Difference between revisions

Revision as of 17:10, 9 August 2021

Latest revision as of 10:21, 19 February 2025

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[[Geminin]] is an important inhibitor of pre-Rc assembly is metazoan cells.<ref name="The Cell Cycle" />

Geminin was identified in a screen for APC/C substrates in ''Xenopus''.<ref name = "Kirschner1998" >{{cite journal |author1=T.J. McGarry |author2=M.W. Kirschner |title=Geminin, an inhibitor of DNA replication, is degraded during mitosis|journal=Cell |volume=93|pages=1043–1053 |year=1998 |doi=10.1016/S0092-8674(00)81209-X |issue= 6 |pmid= 9635433|doi-access=free }}</ref> Studies have shown that Geminin prevents pre_RC assembly by binding to cdt1 and preventing its association with the pre-RC.<ref name = "Dutta2000" >{{cite journal |author1=J.A. Wohlschlegel |author2=B.T. Dwyer |author3=S.K. Dhar |author4=C. Cvetic |author5=J.C. Walter |author6=A. Dutta |title= Inhibition of eukaryotic DNA replication by geminin binding to Cdt1|journal=Science |volume=290|pages=2309–2312 |year=2000 |doi=10.1126/science.290.5500.2309 |issue=5500 |pmid= 11125146}}</ref> Since geminin is degraded by the APC/C, pre-Rc assembly can proceed only when APC/C activity is high, which occurs in G1.<ref name ="Diffley2008" />

The importance of CDKs in preventing re-licensing in metazoan cells is still unclear. Some studies have showedshown that under some conditions, CDKs can also promote licensing. In G0 mammalian cells, APC mediated degradation of Cdc6 prevents licensing. However, when the cells transition into a proliferative state, CDK phosphorylates Cdc6 to stabilizes it and allow it to accumulate and bind to origins before licensing inhibitors such as geminin accumulate.<ref name = "Mailand2005" >{{cite journal |author1=Mailand, N. |author2=Diffley J.F. |title=CDKs promote DNA replication origin licensing in human cells by promoting Cdc6 from APC/C dependent proteolysis |journal=Cell |volume=122|pages=915–926 |year=2005 | doi=10.1016/j.cell.2005.08.013 |issue= 6 |pmid= 16153703|doi-access=free }}</ref>

==Activation of replication origins==