Genetics, Vol. 167, 663-672, June 2004, Copyright © 2004
doi:10.1534/genetics.103.026021

Caenorhabditis elegans lin-35/Rb, efl-1/E2F and Other Synthetic Multivulva Genes Negatively Regulate the Anaphase-Promoting Complex Gene mat-3/APC8

David Garbe1, Jeffrey B. Doto1 and Meera V. Sundaram2

Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6100

2 Corresponding author: Department of Genetics, University of Pennsylvania, 446A Clinical Research Bldg., 415 Curie Blvd., Philadelphia, PA 19104-6145.
E-mail: sundaram{at}mail.med.upenn.edu

Retinoblastoma (Rb)/E2F complexes repress expression of many genes important for G1-to-S transition, but also appear to regulate gene expression at other stages of the cell cycle. In C. elegans, lin-35/Rb and other synthetic Multivulva (SynMuv) group B genes function redundantly with other sets of genes to regulate G1/S progression, vulval and pharyngeal differentiation, and other unknown processes required for viabilty. Here we show that lin-35/Rb, efl-1/E2F, and other SynMuv B genes negatively regulate a component of the anaphase-promoting complex or cyclosome (APC/C). The APC/C is a multisubunit complex that promotes metaphase-to-anaphase progression and G1 arrest by targeting different substrates for ubiquitination and proteasome-mediated destruction. The C. elegans APC/C gene mat-3/APC8 has been defined by temperature-sensitive embryonic lethal alleles that strongly affect germline meiosis and mitosis but only weakly affect somatic development. We describe severe nonconditional mat-3 alleles and a hypomorphic viable allele (ku233), all of which affect postembryonic cell divisions including those of the vulval lineage. The ku233 lesion is located outside of the mat-3 coding region and reduces mat-3 mRNA expression. Loss-of-function alleles of lin-35/Rb and other SynMuv B genes suppress mat-3(ku233) defects by restoring mat-3 mRNA to wild-type levels. Therefore, Rb/E2F complexes appear to repress mat-3 expression.




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