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

Research output: Contribution to journalArticle

62 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)626-631
Number of pages6
JournalEMBO Reports
Volume5
Issue number6
DOIs
StatePublished - Jun 1 2004
Externally publishedYes

Fingerprint

Kinetochores
Yeast
Pathogens
Chromosomes
Fungi
Spindle Apparatus
Saccharomycetales
Chemical activation
RNA
RNA Interference
HeLa Cells
Yeasts
Proteins

Keywords

  • CENP
  • Hec1
  • Kinetochore
  • Mad2
  • Sgt1
  • Spindle checkpoint

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Steensgaard, P., Garrè, M., Muradore, I., Transidico, P., Nigg, E. A., Kitagawa, K., ... Musacchio, A. (2004). Sgt1 is required for human kinetochore assembly. EMBO Reports, 5(6), 626-631. https://doi.org/10.1038/sj.embor.7400154

Sgt1 is required for human kinetochore assembly. / Steensgaard, Peter; Garrè, Massimiliano; Muradore, Ivan; Transidico, Pietro; Nigg, Erich A.; Kitagawa, Katsumi; Earnshaw, William C.; Faretta, Mario; Musacchio, Andrea.

In: EMBO Reports, Vol. 5, No. 6, 01.06.2004, p. 626-631.

Research output: Contribution to journalArticle

Steensgaard, P, Garrè, M, Muradore, I, Transidico, P, Nigg, EA, Kitagawa, K, Earnshaw, WC, Faretta, M & Musacchio, A 2004, 'Sgt1 is required for human kinetochore assembly', EMBO Reports, vol. 5, no. 6, pp. 626-631. https://doi.org/10.1038/sj.embor.7400154
Steensgaard P, Garrè M, Muradore I, Transidico P, Nigg EA, Kitagawa K et al. Sgt1 is required for human kinetochore assembly. EMBO Reports. 2004 Jun 1;5(6):626-631. https://doi.org/10.1038/sj.embor.7400154
Steensgaard, Peter ; Garrè, Massimiliano ; Muradore, Ivan ; Transidico, Pietro ; Nigg, Erich A. ; Kitagawa, Katsumi ; Earnshaw, William C. ; Faretta, Mario ; Musacchio, Andrea. / Sgt1 is required for human kinetochore assembly. In: EMBO Reports. 2004 ; Vol. 5, No. 6. pp. 626-631.
@article{773ad7ba044346f8820722ebd27d97fe,
title = "Sgt1 is required for human kinetochore assembly",
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.",
keywords = "CENP, Hec1, Kinetochore, Mad2, Sgt1, Spindle checkpoint",
author = "Peter Steensgaard and Massimiliano Garr{\`e} and Ivan Muradore and Pietro Transidico and Nigg, {Erich A.} and Katsumi Kitagawa and Earnshaw, {William C.} and Mario Faretta and Andrea Musacchio",
year = "2004",
month = "6",
day = "1",
doi = "10.1038/sj.embor.7400154",
language = "English (US)",
volume = "5",
pages = "626--631",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Sgt1 is required for human kinetochore assembly

AU - Steensgaard, Peter

AU - Garrè, Massimiliano

AU - Muradore, Ivan

AU - Transidico, Pietro

AU - Nigg, Erich A.

AU - Kitagawa, Katsumi

AU - Earnshaw, William C.

AU - Faretta, Mario

AU - Musacchio, Andrea

PY - 2004/6/1

Y1 - 2004/6/1

N2 - 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.

AB - 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.

KW - CENP

KW - Hec1

KW - Kinetochore

KW - Mad2

KW - Sgt1

KW - Spindle checkpoint

UR - http://www.scopus.com/inward/record.url?scp=4344619975&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4344619975&partnerID=8YFLogxK

U2 - 10.1038/sj.embor.7400154

DO - 10.1038/sj.embor.7400154

M3 - Article

C2 - 15133482

AN - SCOPUS:4344619975

VL - 5

SP - 626

EP - 631

JO - EMBO Reports

JF - EMBO Reports

SN - 1469-221X

IS - 6

ER -