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doi:10.1534/genetics.106.059105
A more recent version of this article appeared on January 1, 2007.
REGULAR RESEARCH PAPERS |
Components of the spindle assembly checkpoint regulate the anaphase-promoting complex during meiosis in C. elegans
Kathryn K Stein 1, Ed S Davis 1, Thomas Hays 1 and Andy Golden 1*
1 NIDDK/NIH
* To whom correspondence should be addressed. E-mail: andyg{at}mail.nih.gov.
Submitted on April 7, 2006
Revised on May 4, 2006
Accepted on 12 October 2006
Temperature-sensitive mutations in subunits of the C. elegans Anaphase-Promoting Complex (APC) arrest at metaphase of meiosis I at the restrictive temperature. Embryos depleted of the APC co-activator, FZY-1, by RNAi also arrest at this stage. To identify regulators and potential substrates of the APC, we performed a genetic suppressor screen with a weak allele of the APC subunit MAT-3/CDC23/APC8, whose defects are specific to meiosis. Twenty-seven suppressors were isolated that resulted in embryonic viability and larval development at the restrictive temperature. We have identified the molecular lesions in 18 of these suppressors, which correspond to five genes. In addition to a single intragenic suppressor, we found mutations in the APC co-activator fzy-1 and in three spindle assembly checkpoint genes, mdf-1, mdf-2, and mdf-3/san-1, orthologs of Mad1, Mad2, and Mad3 respectively. Reduction-of-function alleles of mdf-2 and mdf-3 suppress APC mutants and exhibit pleiotropic phenotypes in an otherwise wild-type background. Analysis of a single separation-of-function allele of mdf-1 suggests that MDF-1 has a dual role during development. These studies provide evidence that components of the spindle assembly checkpoint may regulate the metaphase-to-anaphase transition in the absence of spindle damage during C. elegans meiosis.
Key Words: anaphase-promoting complex, meiosis, spindle assembly checkpoint
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