CDKs promote DNA replication origin licensing in human cells by protecting Cdc6 from APC/C-dependent proteolysis

Article Abstract:

Cyclin-dependent kinases (CDKs) phosphorylation of the essential licensing factor Cdc6 stabilizes it by preventing its association with the anaphase promoting complex/cyclosome (APC/C). APC/C-dependent Cdc6 proteolysis prevents pre-RC assembly in quiescent cells and when cells reenter the cell cycle from quiescence, CDK-dependent Cdc6 stabilization allows Cdc6 to accumulate before the licensing inhibitors geminin and cylcin A which are also APC/C substrates.

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Systems-level dissection of the cell-cycle oscillator: Bypassing positive feedback produces damped oscillations

Article Abstract:

The short-circuiting positive- feedback make the oscillations in Cdc2 activity faster, less temporally abrupt, and damped, and also compromises the activation of cyclin destruction, interfering with mitotic exit and DNA replication. The results underscore the fundamental similarity of cell-cycle oscillations in embryo to repetitive action potentials in pacemaker neurons, with both systems relying on a combination of negative and positive-feedback loops.

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CDKs give Cdc6 a license to drive into S phase

Article Abstract:

The phosphorylation of Cdc6 by cyclin-dependent kinases prevents its destruction by the anaphase promoting complex (APC). The simple mechanism explains how the APC simultaneously spares Cdc6 while targeting for destruction suppresors of DNA replication during the transition from quiescence to cell cycle reentry.

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