Premature Sister Chromatid Separation Is Poorly Detected by the Spindle Assembly Checkpoint as a Result of System-Level Feedback

Sister chromatid cohesion, mediated by the cohesin complex, is essential for faithful mitosis. Nevertheless, evidence suggests that the surveillance mechanism that governs mitotic fidelity, the spindle assembly checkpoint (SAC), is not robust enough to halt cell division when cohesion loss occurs prematurely. The mechanism behind this poor response is not properly understood. Using developing Drosophila brains, we show that full sister chromatid separation elicits a weak checkpoint response resulting in abnormal mitotic exit after a short delay. Quantitative live-cell imaging approaches combined with mathematical modeling indicate that weak SAC activation upon cohesion loss is caused by weak signal generation. This is further attenuated by several feedback loops in the mitotic signaling network. We propose that multiple feedback loops involving cyclin-dependent kinase 1 (Cdk1) gradually impair error-correction efficiency and accelerate mitotic exit upon premature loss of cohesion. Our findings explain how cohesion defects may escape SAC surveillance.

Integrated traffic simulation model - phase I. Volume 2: design of the TRAF system (TOS). Final report.

Federal Highway Administration, Washington, D.C.

Problems associated with the statutory requirements for design of the interstate system to accommondate traffic forecast for the year 1975.

Mode of access: Internet.

Integrated motorist information system (IMIS) feasibility and design study. Phase I: feasibility study. Volume 2 - appendices. Final report.

Federal Highway Administration, Office of Research and Development, Washington, D.C.

National Accident Sampling System sample design - phases 2 and 3 - executive summary. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

National Accident Sampling System sample design - phases 2 and 3. Volume II: exhibits. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

National Accident Sampling System sample design - phases 2 and 3. Volume I: final technical report.

National Highway Traffic Safety Administration, Washington, D.C.

An experimental evaluation of the 1969 Volkswagen 1500 restraint system and front seat assembly.

National Highway Safety Bureau, Washington, D.C.

Final design and implementation plan for evaluating the effectiveness of FMVSS 301: fuel system integrity. Tasks #4 & #5 report.

National Highway Traffic Safety Administration, Washington, D.C.

Integrated motorist information system (IMIS) feasibility and design study. Phase I: feasibility study. Volume 1 - final report.

Federal Highway Administration, Office of Research and Development, Washington, D.C.

Integrated motorist information system (IMIS) feasibility and design study. Phase I: feasibility study. Volume 3 - executive summary. Final report.

Federal Highway Administration, Office of Research and Development, Washington, D.C.

Lock design, sidewall port filling and emptying system : final report /

"Ju;y 1975."

System definition report for the National Driver Register Design Study. Interim report.

National Highway Traffic Safety Administration, Traffic Safety Programs, Washington, D.C.

Vehicle design optimization system user manual. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Hardware design of a real-time musical system /

Includes bibliographical references.