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Updated: Feb 28, 2026

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis
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Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis

Published on: December 5, 2017

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MLL/WDR5 Complex Regulates Kif2A Localization to Ensure Chromosome Congression and Proper Spindle Assembly during

Aamir Ali1, Sailaja Naga Veeranki2, Akash Chinchole1

  • 1Laboratory of Cell Cycle Regulation, Centre for DNA Fingerprinting and Diagnostics (CDFD), Nampally, Hyderabad 500001, India; Graduate Studies, Manipal University, Manipal, India.

Developmental Cell
|June 21, 2017
PubMed

Insights

The Mixed-lineage leukemia (MLL) complex has a novel role in cell division, localizing to the mitotic spindle. This function is crucial for proper chromosome segregation and spindle formation, impacting chromosomal stability.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • The Mixed-lineage leukemia (MLL) complex, comprising WDR5, RbBP5, ASH2L, and DPY30, is known for catalyzing H3K4 trimethylation and gene activation.
  • Its role in mitosis has not been fully elucidated, particularly outside of its chromatin-modifying functions.

Purpose of the Study:

  • To investigate the non-canonical functions of the MLL complex during mitosis.
  • To characterize the interaction of the MLL complex with mitotic machinery, specifically microtubule-associated motor proteins.

Main Methods:

  • RNA interference (RNAi) to assess loss-of-function effects of the MLL complex.
  • Immunofluorescence microscopy to determine the localization of MLL and WDR5 during mitosis.
  • Co-immunoprecipitation assays to identify interacting partners of the MLL complex, including kinesin and dynein motors.
  • Analysis of Kif2A localization and function in MLL-depleted cells.

Main Results:

  • The MLL complex and WDR5 were found to localize to the mitotic spindle apparatus.
  • Loss of MLL complex function led to defects in chromosome congression and spindle formation.
  • The MLL complex interacts with Kif2A, a microtubule depolymerase, and regulates its spindle localization.
  • A conserved WDR5 interaction (Win) motif in Kif2A mediates its direct interaction with WDR5 for spindle localization.

Conclusions:

  • The MLL complex plays a critical, chromatin-independent role in mitosis by regulating the spindle localization of Kif2A.
  • This novel mitotic function of the MLL complex is essential for proper chromosome segregation and spindle integrity.
  • Dysregulation of this MLL function may contribute to chromosomal instability observed in cancers.
Keywords:
Kif2AMLLWDR5Win motifkinesinmitosis

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