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Updated: Aug 9, 2026

Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
Published on: September 28, 2012
The 8-kDa dynein light chain binds to p53-binding protein 1 and mediates DNA damage-induced p53 nuclear accumulation
Kevin W-H Lo1, Ho-Man Kan, Ling-Nga Chan
1Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, People's Republic of China.
Abstract:
The tumor suppressor protein p53 is known to undergo cytoplasmic dynein-dependent nuclear translocation in response to DNA damage. However, the molecular link between p53 and the minus end-directed microtubule motor dynein complex has not been described. We report here that the 8-kDa light chain (LC8) of dynein binds to p53-binding protein 1 (53BP1). The LC8-binding domain was mapped to a short peptide segment immediately N-terminal to the kinetochore localization region of 53BP1. The LC8-binding domain is completely separated from the p53-binding domain in 53BP1. Therefore, 53BP1 can potentially act as an adaptor to assemble p53 to the dynein complex. Unlike other known LC8-binding proteins, 53BP1 contains two distinct LC8-binding motifs that are arranged in tandem. We further showed that 53BP1 can directly associate with the dynein complex. Disruption of the interaction between LC8 and 53BP1 in vivo prevented DNA damage-induced nuclear accumulation of p53. These data illustrate that LC8 is able to function as a versatile acceptor to link a wide spectrum of molecular cargoes to the dynein motor.
Insights
The 8-kDa light chain (LC8) of dynein binds to p53-binding protein 1 (53BP1), acting as a crucial link. This interaction is essential for the nuclear translocation of tumor suppressor p53 following DNA damage.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The tumor suppressor protein p53 translocates to the nucleus upon DNA damage, a process dependent on cytoplasmic dynein.
- The precise molecular mechanism connecting p53 to the dynein motor complex remains unclear.
Purpose of the Study:
- To elucidate the molecular link between p53 and the dynein motor complex.
- To investigate the role of p53-binding protein 1 (53BP1) in this interaction.
Main Methods:
- Protein binding assays to map the LC8-binding domain on 53BP1.
- In vivo experiments to disrupt the LC8-53BP1 interaction and observe effects on p53 nuclear accumulation.
Main Results:
- The 8-kDa light chain (LC8) of dynein binds to 53BP1, specifically to a domain N-terminal to its kinetochore localization region.
- 53BP1 contains two tandem LC8-binding motifs and directly associates with the dynein complex.
- Disrupting the LC8-53BP1 interaction in vivo inhibited DNA damage-induced nuclear accumulation of p53.
Conclusions:
- 53BP1 acts as an adaptor, linking p53 to the dynein complex via LC8.
- LC8 functions as a versatile molecular adaptor, connecting various cargoes to the dynein motor.
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