The 3M Complex Maintains Microtubule and Genome Integrity

Jun Yan, Feng Yan, Zhijun Li, Becky Sinnott, Kathryn M. Cappell, Yanbao Yu, Jinyao Mo, Joseph A. Duncan, Xian Chen, Valerie Cormier-Daire, Angelique W. Whitehurst, Yue Xiong

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

CUL7, OBSL1, and CCDC8 genes are mutated in a mutually exclusive manner in 3M and other growth retardation syndromes. The mechanism underlying the function of the three 3M genes in development is not known. We found that OBSL1 and CCDC8 form a complex with CUL7 and regulate the level and centrosomal localization of CUL7, respectively. CUL7 depletion results in altered microtubule dynamics, prometaphase arrest, tetraploidy, and mitotic cell death. These defects are recaptured in CUL7 mutated 3M cells and can be rescued by wild-type, but not by 3M patient-derived CUL7 mutants. Depletion of either OBSL1 or CCDC8 results in defects and sensitizes cells to microtubule damage similarly to loss of CUL7 function. Microtubule damage reduces the level of CCDC8 that is required for the centrosomal localization of CUL7. We propose that CUL7, OBSL1, and CCDC8 proteins form a 3M complex that functions in maintaining microtubule and genome integrity and normal development.

Original languageEnglish (US)
Pages (from-to)791-804
Number of pages14
JournalMolecular cell
Volume54
Issue number5
DOIs
StatePublished - Jun 5 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Yan, J., Yan, F., Li, Z., Sinnott, B., Cappell, K. M., Yu, Y., Mo, J., Duncan, J. A., Chen, X., Cormier-Daire, V., Whitehurst, A. W., & Xiong, Y. (2014). The 3M Complex Maintains Microtubule and Genome Integrity. Molecular cell, 54(5), 791-804. https://doi.org/10.1016/j.molcel.2014.03.047