Genetics, Vol 147, 1743-1753, Copyright © 1997

INVESTIGATIONS

Drosophila Male-Specific Lethal-2 Protein: Structure/Function Analysis and Dependence on MSL-1 for Chromosome Association

L. M. Lyman, K. Copps, L. Rastelli, R. L. Kelley and M. I. Kuroda
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030

MSL-2 is required for the male-specific assembly of a dosage compensation regulatory complex on the X chromosome of Drosophila melanogaster. We found that MSL-2 binds in a reproducible, partial pattern to the male X chromosome in the absence of MLE or MSL-3, or when ectopically expressed at a low level in females. Moreover, the pattern of MSL-2 binding corresponds precisely in each case to that of MSL-1, suggesting that the two proteins function together to associate with the X. Consistent with this hypothesis, we isolated EMS-induced loss of function msl-1 and msl-2 alleles in a screen for suppressors of the toxic effects of MSL-2 expression in females. We also used site-directed mutagenesis to determine the importance of the MSL-2 RING finger domain and second cysteine-rich motif. The mutations, including those in conserved zinc coordinating cysteines, confirm that the RING finger is essential for MSL-2 function, while suggesting a less stringent requirement for an intact second motif.

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