Nuclear localization of Desmoplakin and its involvement in telomere maintenance

UM > Faculty of Health Sciences > DEPARTMENT OF BIOMEDICAL SCIENCES

Status	已發表Published
	Nuclear localization of Desmoplakin and its involvement in telomere maintenance
	LI, PP; MENG, Y; WANG, Y; LI, JJ; Wang, L.; Di, L.
	2019-05-01
Source Publication	Int. J. Biol. Sci.
ISSN	1449-2288
Pages	2350-2362
Abstract	The interaction between genomic DNA and protein fundamentally determines the activity and the function of DNA elements. Capturing the protein complex and identifying the proteins associated with a specific DNA locus is difficult. Herein, we employed CRISPR, the well-known gene-targeting tool in combination with the proximity-dependent labeling tool BioID to capture a specific genome locus associated proteins and to uncover the novel functions of these proteins. By applying this research tool on telomeres, we identified DSP, out of many others, as a convincing telomere binding protein validated by both biochemical and cell-biological approaches. We also provide evidence to demonstrate that the C-terminal domain of DSP is required for its binding to telomere after translocating to the nucleus mediated by NLS sequence of DSP. In addition, we found that the telomere binding of DSP is telomere length dependent as hTERT inhibition or knockdown caused a decrease of telomere length and diminished DSP binding to the telomere. Knockdown of TRF2 also negatively influenced DSP binding to the telomere. Functionally, loss of DSP resulted in the shortened telomere DNA and induced the DNA damage response and cell apoptosis. In conclusion, our studies identified DSP as a novel potential telomere binding protein and highlighted its role in protecting against telomere DNA damage and resultant cell apoptosis.
Keyword	CRISPR BioID telomere DSP
Language	英語English
The Source to Article	PB_Publication
PUB ID	45482
Document Type	Journal article
Collection	DEPARTMENT OF BIOMEDICAL SCIENCES
Corresponding Author	Wang, L.; Di, L.
Recommended Citation GB/T 7714	LI, PP,MENG, Y,WANG, Y,et al. Nuclear localization of Desmoplakin and its involvement in telomere maintenance[J]. Int. J. Biol. Sci., 2019, 2350-2362.
APA	LI, PP., MENG, Y., WANG, Y., LI, JJ., Wang, L.., & Di, L. (2019). Nuclear localization of Desmoplakin and its involvement in telomere maintenance. Int. J. Biol. Sci., 2350-2362.
MLA	LI, PP,et al."Nuclear localization of Desmoplakin and its involvement in telomere maintenance".Int. J. Biol. Sci. (2019):2350-2362.

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