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Lesions in many different spindle components activate the spindle checkpoint in the budding yeast Saccharomyces
K G Hardwick1, R Li, C Mistrot
1Department of Physiology, University of California, San Francisco, California 94143-0444, USA.
Abstract:
The spindle checkpoint arrests cells in mitosis in response to defects in the assembly of the mitotic spindle or errors in chromosome alignment. We determined which spindle defects the checkpoint can detect by examining the interaction of mutations that compromise the checkpoint (mad1, mad2, and mad3) with those that damage various structural components of the spindle. Defects in microtubule polymerization, spindle pole body duplication, microtubule motors, and kinetochore components all activate the MAD-dependent checkpoint. In contrast, the cell cycle arrest caused by mutations that induce DNA damage (cdc13), inactivate the cyclin proteolysis machinery (cdc16 and cdc23), or arrest cells in anaphase (cdc15) is independent of the spindle checkpoint.
Insights
The spindle checkpoint ensures proper cell division by halting mitosis when the spindle assembly or chromosome alignment is faulty. This study identifies specific spindle defects that trigger this crucial cell cycle control mechanism.
Area of Science:
- Cell Biology
- Genetics
- Molecular Biology
Background:
- The spindle checkpoint is a critical cell cycle surveillance mechanism that prevents aneuploidy.
- It arrests cells in mitosis when errors in spindle assembly or chromosome alignment occur.
Purpose of the Study:
- To determine the specific types of spindle defects that the spindle checkpoint can detect.
- To differentiate between checkpoint-dependent and checkpoint-independent cell cycle arrests.
Main Methods:
- Utilized genetic analysis by examining the interactions between mutations affecting the spindle checkpoint (mad1, mad2, mad3) and mutations impacting spindle components.
- Assessed cell cycle arrest phenotypes in response to various induced cellular defects.
Main Results:
- The spindle checkpoint, dependent on MAD proteins, is activated by defects in microtubule polymerization, spindle pole body duplication, microtubule motors, and kinetochore components.
- Cell cycle arrests caused by DNA damage (cdc13), defects in cyclin proteolysis (cdc16, cdc23), or anaphase progression errors (cdc15) are independent of the spindle checkpoint.
Conclusions:
- The spindle checkpoint specifically monitors the integrity of spindle assembly and chromosome attachment.
- This provides a detailed understanding of the regulatory scope of the spindle checkpoint in mitosis.