Control of centromere localization of the MEI-S332 cohesion protection protein.
In mitosis and meiosis, cohesion is maintained at the centromere until sister-chromatid separation. Drosophila MEI-S332 is essential for centromeric cohesion in meiosis and contributes to, though is not absolutely required for, cohesion in mitosis. It localizes specifically to centromeres in prometaphase and delocalizes at the metaphase-anaphase transition. In mei-S332 mutants, centromeric sister-chromatid cohesion is lost at anaphase I, giving meiosis II missegregation. MEI-S332 is the founding member of a family of proteins important for chromosome segregation. One likely activity of these proteins is to protect the cohesin subunit Rec8 from cleavage at the metaphase I-anaphase I transition. Although the family members do not show high sequence identity, there are two short stretches of homology, and mutations in conserved residues affect protein function. Here we analyze the cis- and trans-acting factors required for MEI-S332 localization. We find a striking correlation between domains necessary for MEI-S332 centromere localization and conserved regions within the protein family. Drosophila MEI-S332 expressed in human cells localizes to mitotic centromeres, further highlighting this functional conservation. MEI-S332 can localize independently of cohesin, assembling even onto unreplicated chromatids. However, the separase pathway that regulates cohesin dissociation is needed for MEI-S332 delocalization at anaphase.
Whitehead Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Janice Y
JY
Lee
Kimberley J
KJ
Dej
Jacqueline M
JM
Lopez
Terry L
TL
Orr-Weaver
D000818:Animals; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D002503:Centromere / Q000378:metabolism / Q000502:physiology*; D002842:Chromatids / Q000378:metabolism* / Q000502:physiology; D002868:Chromosomal Proteins, Non-Histone; D020090:Chromosome Segregation / Q000502:physiology*; D017931:DNA Primers; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D010450:Endopeptidases / Q000378:metabolism; D005656:Fungal Proteins; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins; D008856:Microscopy, Fluorescence; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D064247:Separase; D014162:Transfection; D000097722:Cohesins
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D017931:DNA Primers; D029721:Drosophila Proteins; D010450:Endopeptidases; D005656:Fungal Proteins; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D009687:Nuclear Proteins; D064247:Separase; D000097722:Cohesins; C096223:mei-S332 protein, Drosophila; C577987:ESPL1 protein, human; C577989:Sse protein, Drosophila