The pseudo GTPase CENP-M drives human kinetochore assembly.
Elife
; 3: e02978, 2014 Jul 08.
Article
en En
| MEDLINE
| ID: mdl-25006165
ABSTRACT
Kinetochores, multi-subunit complexes that assemble at the interface with centromeres, bind spindle microtubules to ensure faithful delivery of chromosomes during cell division. The configuration and function of the kinetochore-centromere interface is poorly understood. We report that a protein at this interface, CENP-M, is structurally and evolutionarily related to small GTPases but is incapable of GTP-binding and conformational switching. We show that CENP-M is crucially required for the assembly and stability of a tetramer also comprising CENP-I, CENP-H, and CENP-K, the HIKM complex, which we extensively characterize through a combination of structural, biochemical, and cell biological approaches. A point mutant affecting the CENP-M/CENP-I interaction hampers kinetochore assembly and chromosome alignment and prevents kinetochore recruitment of the CENP-T/W complex, questioning a role of CENP-T/W as founder of an independent axis of kinetochore assembly. Our studies identify a single pathway having CENP-C as founder, and CENP-H/I/K/M and CENP-T/W as CENP-C-dependent followers.DOI http//dx.doi.org/10.7554/eLife.02978.001.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas Nucleares
/
Proteínas Cromosómicas no Histona
/
Cinetocoros
/
GTP Fosfohidrolasas
Límite:
Humans
Idioma:
En
Revista:
Elife
Año:
2014
Tipo del documento:
Article
País de afiliación:
Italia