Stable hZW10 kinetochore residency, mediated by hZwint-1 interaction, is essential for the mitotic checkpoint

Jakub K. Famulski, Larissa Vos, Xuejun Sun, Gordon Chan

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

The mitotic checkpoint is an essential surveillance mechanism that ensures high fidelity chromosome segregation during mitosis. Mitotic checkpoint function depends on numerous kinetochore proteins, including ZW10, ROD, and Zwilch (the ROD-ZW10-Zwilch complex). Through an extensive mutagenesis screen of hZW10, we have mapped the kinetochore localization domain of hZW10 as well as the hZwint-1 interaction domain. We find that hZwint-1 - noninteracting mutants still localize to kinetochores. In addition, using fluorescence recovery after photobleaching, we have found that hZW10 residency at metaphase kinetochores is brief (half-time of 13 s). However, during prometaphase or at unattached kinetochores, enhanced green fluorescent protein - hZW10 becomes a stable component of the kinetochore. Moreover, we find that stable hZW10 kinetochore residency at prometaphase kinetochores is dependent on its interaction with hZwint-1, and is essential for mitotic checkpoint arrest.

Original languageEnglish
Pages (from-to)507-520
Number of pages14
JournalJournal of Cell Biology
Volume180
Issue number3
DOIs
StatePublished - Feb 11 2008

ASJC Scopus subject areas

  • Cell Biology

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