Sgt1 is required for human kinetochore assembly.

Peter Steensgaard, Massimiliano Garrè, Ivan Muradore, Pietro Transidico, Erich A Nigg, Katsumi Kitagawa, William C Earnshaw, Mario Faretta, Andrea Musacchio

Journal: EMBO reports 2005;5(6):626-31

PMID: 15133482

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Abstract

Budding yeast Sgt1 is required for kinetochore assembly, and its homologues have a role in cAMP signalling in fungi and pathogen resistance in plants. The function of mammalian Sgt1 is unknown. We report that RNA interference-mediated depletion of Sgt1 from HeLa cells causes dramatic alterations of the mitotic spindle and problems in chromosome alignment. Cells lacking Sgt1 undergo a mitotic delay due to activation of the spindle checkpoint. The checkpoint response, however, is significantly weakened in Sgt1-depleted cells, and this correlates with a dramatic reduction in kinetochore levels of Mad1, Mad2 and BubR1. These effects are explained by a problem in kinetochore assembly that prevents the localization of Hec1, CENP-E, CENP-F, CENP-I, but not CENP-C, to mitotic kinetochores. Our studies implicate Sgt1 as an essential protein and a critical assembly factor for the mammalian kinetochore, and lend credit to the hypothesis of a kinetochore assembly pathway that is conserved from yeast to man.

Address: Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.

DOI: 10.1038/sj.embor.7400154

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MeSH Terms: Calcium-Binding Proteins, Cell Cycle Proteins, Centromere, Chromosomal Proteins, Non-Histone, DNA-Binding Proteins, HeLa Cells, Humans, Kinetochores, Mad2 Proteins, Mitosis, Nuclear Proteins, Phosphoproteins, Protein Kinases, Protein Serine-Threonine Kinases, RNA Interference, RNA, Small Interfering, Repressor Proteins, Spindle Apparatus