Journal article
Vimentin intermediate filaments orchestrate DNA nonhomologous end joining repair and lipolysis after DNA damage
Oncogene, Vol.44(33), pp.3025-3036
09/01/2025
DOI: 10.1038/s41388-025-03465-2
PMID: 40550847
Abstract
Vimentin is a major component of intermediate filaments (IFs) within the three cytoskeletal systems, alongside actin filaments and microtubules. Spanning from the plasma membrane to the nuclear lamina, vimentin IFs form a cage-like network surrounding the nucleus, and modulate cell mechanics, migration and signaling. In this study, we show that vimentin depletion leads to accumulation of endogenous DNA damage. Interestingly, vimentin is associated with Ku proteins that sense DNA double strand breaks (DSB) and mediate nonhomologous end joining (NHEJ) repair. Depletion of vimentin impairs NHEJ repair, in line with reduced recruitment of Ku proteins to DNA damage sites and deficient activation of DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Beyond its involvement in DSB repair, our research also uncovers the role of vimentin in modulating lipolysis following DNA damage. We show that DNA damage reduces lipid droplet contents via adipose triglyceride lipase (ATGL). Vimentin binds to and suppresses ATGL in lipolysis. Moreover, DNA-PKcs modulates ATGL and DNA damage-induced lipolysis via vimentin. Targeting vimentin leads to DNA damage hypersensitivity, suggesting its potential in cancer therapy. Taken together, our findings elucidate new roles of vimentin in orchestrating DNA repair and lipolysis, shedding light on the involvement of vimentin IF in cell homeostasis, cancer resistance, and metabolic regulation.
Details
- Title: Subtitle
- Vimentin intermediate filaments orchestrate DNA nonhomologous end joining repair and lipolysis after DNA damage
- Creators
- Feifei Wang - Anhui UniversityMengtao Rong - Anhui UniversityLiang Zhang - Jiujiang UniversityAbhishikt D Solomon - University of North Carolina at Chapel HillWenli Gui - Anhui UniversityJuan Li - Anhui UniversityRenqing Wang - First Affiliated Hospital of Anhui Medical UniversityJiajing Wu - Anhui UniversityLing Wang - University of North Carolina at Chapel HillXingyuan Yang - Anhui UniversityAimin Peng - University of North Carolina at Chapel Hill
- Resource Type
- Journal article
- Publication Details
- Oncogene, Vol.44(33), pp.3025-3036
- DOI
- 10.1038/s41388-025-03465-2
- PMID
- 40550847
- NLM abbreviation
- Oncogene
- ISSN
- 1476-5594
- eISSN
- 1476-5594
- Publisher
- SPRINGERNATURE
- Grant note
- 32400595 / National Natural Science Foundation of China (National Science Foundation of China)
- Language
- English
- Electronic publication date
- 06/23/2025
- Date published
- 09/01/2025
- Academic Unit
- Dental Research
- Record Identifier
- 9984833632802771
Metrics
1 Record Views