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Nuclear localization of Desmoplakin and its involvement in telomere maintenance
Peipei Li1; Yuan Meng1; Yuan Wang; Jingjing Li; Manting Lam2; Li Wang1,2; Li-jun Di1
2019-08-24
Source PublicationINTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
ISSN1449-2288
Volume15Issue:11Pages: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.

KeywordCrispr Bioid Telomere Dsp
DOI10.7150/ijbs.34450
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics
WOS SubjectBiochemistry & Molecular Biology ; Biology
WOS IDWOS:000485655300007
PublisherIVYSPRING INT PUBL, PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA
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Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorLi Wang; Li-jun Di
Affiliation1.Cancer Center, Faculty of Health Sciences, University of Macau, Macau, SAR of China
2.Metabolomics Core, Faculty of Health Sciences, University of Macau, Macau, SAR of China
First Author AffilicationFaculty of Health Sciences
Corresponding Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Peipei Li,Yuan Meng,Yuan Wang,et al. Nuclear localization of Desmoplakin and its involvement in telomere maintenance[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2019,15(11):2350-2362.
APA Peipei Li.,Yuan Meng.,Yuan Wang.,Jingjing Li.,Manting Lam.,...&Li-jun Di.(2019).Nuclear localization of Desmoplakin and its involvement in telomere maintenance.INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,15(11),2350-2362.
MLA Peipei Li,et al."Nuclear localization of Desmoplakin and its involvement in telomere maintenance".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 15.11(2019):2350-2362.
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