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Updated: Dec 31, 2025

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
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Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins

Published on: September 28, 2012

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RAD50 regulates mitotic progression independent of DNA repair functions

Lea Völkening1, Anna Vatselia1, Girmay Asgedom2

  • 1Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|January 8, 2020
PubMed

Insights

RAD50 deficiency causes significant delays in cell mitosis, independent of its DNA repair role. This mitotic progression defect in RAD50-deficient cells can be restored by introducing RAD50.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • The Mre11A/RAD50/NBN (MRN) complex is crucial for DNA double-strand break (DSB) repair.
  • Emerging evidence suggests the MRN complex may also influence mitosis duration.

Purpose of the Study:

  • To investigate the role of RAD50 in mitotic progression.
  • To determine if RAD50's function in mitosis is separable from its DNA repair functions.

Main Methods:

  • Utilized RAD50-deficient fibroblasts and live cell imaging with GFP-labeled H2B.
  • Performed complementation assays with RAD50 phosphorylation mutants.
  • Investigated effects of ATM, NBN, MRE11A, and ATR inhibitors on mitotic progression.

Main Results:

  • RAD50-deficient fibroblasts showed a marked delay throughout all mitotic phases, which was rescued by RAD50 transduction.
  • RAD50 phosphorylation at Ser635 had minimal impact on mitotic progression.
  • Deficiencies in ATM or NBN, and nuclease-deficient MRE11A, did not significantly slow mitosis.
  • ATR kinase inhibition prolonged mitosis, largely independent of RAD50 status.

Conclusions:

  • RAD50 plays a distinct role in regulating mitotic progression, separate from its established DNA repair functions.
  • Mitotic delay in RAD50-deficient cells highlights a novel function of this complex component.
Keywords:
ATRMRN complexRAD50 phosphorylationcell divisionmitotic delay

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