2. Academic Validation
  3. DNA damage promotes microtubule dynamics through a DNA-PK-AKT axis for enhanced repair

DNA damage promotes microtubule dynamics through a DNA-PK-AKT axis for enhanced repair

  • J Cell Biol. 2021 Feb 1;220(2):e201911025. doi: 10.1083/jcb.201911025.
Shuyun Ma 1 2,  Zeming Rong 1 2,  Chen Liu 1 2,  Xiaobing Qin 1 2,  Xiaoyan Zhang 3 4,  Qiang Chen 1 2
Affiliations

Affiliations

  • 1 Department of Radiation and Medical Oncology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
  • 2 Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, China.
  • 3 College of Biomedicine and Health, Huazhong Agricultural University, Wuhan, China.
  • 4 College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
PMID: 33404607 DOI: 10.1083/jcb.201911025
Abstract

DNA double-strand breaks (DSBs) are mainly repaired by c-NHEJ and HR pathways. The enhanced DSB mobility after DNA damage is critical for efficient DSB repair. Although microtubule dynamics have been shown to regulate DSB mobility, the reverse effect of DSBs to microtubule dynamics remains elusive. Here, we uncovered a novel DSB-induced microtubule dynamics stress response (DMSR), which promotes DSB mobility and facilitates c-NHEJ repair. DMSR is accompanied by interphase centrosome maturation, which occurs in a DNA-PK-AKT-dependent manner. Depletion of PCM proteins attenuates DMSR and the mobility of DSBs, resulting in delayed c-NHEJ. Remarkably, DMSR occurs only in G1 or G0 cells and lasts around 6 h. Both inhibition of DNA-PK and depletion of 53BP1 abolish DMSR. Taken together, our study reveals a positive DNA repair mechanism in G1 or G0 cells in which DSBs actively promote microtubule dynamics and facilitate the c-NHEJ process.

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