Mitosis-specific MRN complex promotes a mitotic signaling cascade to regulate spindle dynamics and chromosome segregation

Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):E10079-E10088. doi: 10.1073/pnas.1806665115. Epub 2018 Oct 8.


The MRE11-RAD50-NBS1 (MRN) complex is well known for participating in DNA damage response pathways in all phases of cell cycle. Here, we show that MRN constitutes a mitosis-specific complex, named mMRN, with a protein, MMAP. MMAP directly interacts with MRE11 and is required for optimal stability of the MRN complex during mitosis. MMAP colocalizes with MRN in mitotic spindles, and MMAP-deficient cells display abnormal spindle dynamics and chromosome segregation similar to MRN-deficient cells. Mechanistically, both MMAP and MRE11 are hyperphosphorylated by the mitotic kinase, PLK1; and the phosphorylation is required for assembly of the mMRN complex. The assembled mMRN complex enables PLK1 to interact with and activate the microtubule depolymerase, KIF2A, leading to spindle turnover and chromosome segregation. Our study identifies a mitosis-specific version of the MRN complex that acts in the PLK1-KIF2A signaling cascade to regulate spindle dynamics and chromosome distribution.

Keywords: C2ORF44; KIF2A; MMAP; MRN; mMRN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Chromosome Segregation / physiology*
  • DNA-Binding Proteins / metabolism*
  • HCT116 Cells
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Kinesins / metabolism
  • MRE11 Homologue Protein / metabolism*
  • Microtubules / metabolism
  • Mitosis / physiology*
  • Nuclear Proteins / metabolism*
  • Phosphorylation / physiology
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Spindle Apparatus / metabolism
  • Spindle Apparatus / physiology*


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Protein Serine-Threonine Kinases
  • polo-like kinase 1
  • MRE11 Homologue Protein
  • Kinesins