کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2040014 1073094 2015 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Premature Sister Chromatid Separation Is Poorly Detected by the Spindle Assembly Checkpoint as a Result of System-Level Feedback
ترجمه فارسی عنوان
جداسازی کروماتیک خواهر نارس به وسیله بازرسی مونتاژ اسپیندل به عنوان نتیجه بازخورد سیستم سطح
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
چکیده انگلیسی


• Precocious sister chromatid separation does not elicit robust SAC activation
• Error-correction efficiency declines gradually upon premature cohesion loss
• Mitotic exit in the absence of cohesin is accelerated by multiple feedback loops
• Cells with premature sister chromatid separation are ultrasensitive to Cdk1 inhibition

SummarySister 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.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 13, Issue 3, 20 October 2015, Pages 469–478
نویسندگان
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