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Regulation of XPC Binding Dynamics and Global Nucleotide Excision Repair by p63 and Vitamin D Receptor
J Phys Chem B. 2023 Mar 6. doi: 10.1021/acs.jpcb.2c07257. Online ahead of print.ABSTRACTp63 and the vitamin D receptor (VDR) play important roles in epidermal development and differentiation, but their roles and relationship in the response to ultraviolet (UV) radiation are less clear. Using TERT-immortalized human keratinocytes expressing shRNA targeting p63 in concert with exogenously applied siRNA targeting VDR, we assessed p63 and VDR's separate and combined effect on nucleotide excision repair (NER) of UV-induced 6-4 photoproducts (6-4PP). Knockdown of p63 reduced VDR and XPC expression relative to nontargeting contro...
Source: Health Physics - March 6, 2023 Category: Physics Authors: Christian T Wong Katherine Ona Dennis H Oh Source Type: research

622 Regulation of XPC binding dynamics and global nucleotide excision repair by p63 and vitamin D receptor
p63 and the vitamin D receptor (VDR) play important roles in epidermal development and differentiation, but their roles and relationship in the response to ultraviolet (UV) radiation are unclear. Using TERT-immortalized human keratinocytes expressing shRNA targeting p63 in concert with exogenously applied siRNA targeting VDR, we assessed p63 and VDR ’s separate and combined effect on nucleotide excision repair (NER) of UV-induced 6-4 photoproducts (6-4PP) with a focus on the XPC DNA damage recognition protein.
Source: Journal of Investigative Dermatology - July 20, 2022 Category: Dermatology Authors: C. Wong, D.H. Oh Source Type: research

Vitamin D receptor promotes global nucleotide excision repair by facilitating XPC dissociation from damaged DNA
Vitamin D receptor (VDR) is important for normal DNA repair though the mechanism by which it acts is unclear. Following focal ultraviolet irradiation to create subnuclear spots of DNA damage, epidermal keratinocytes from VDR-null mice as well as human epidermal keratinocytes depleted of VDR with siRNA removed pyrimidine(6-4)pyrimidone photoproducts more slowly than control cells. Co-staining with antibodies to XPC, the DNA damage recognition sensor which initiates nucleotide excision repair, revealed that XPC rapidly accumulated at spots of damage and gradually faded in control human keratinocytes.
Source: Journal of Investigative Dermatology - January 28, 2021 Category: Dermatology Authors: Christian T. Wong, Dennis H. Oh Tags: Original Article Source Type: research

643 XPC dissociation from damaged DNA and efficient global nucleotide excision repair depend on vitamin D receptor
Vitamin D and its receptor, VDR, together and independently, have been associated with DNA repair, though the mechanism by which they act is unclear. Upon ultraviolet irradiation through 3 mm pores in otherwise opaque filters to create focal spots of DNA damage, epidermal keratinocytes from both VDR-null mice and human keratinocytes depleted of VDR with siRNA exhibited slower removal of 6-4 photoproducts than normal control cells over 90 minutes. Co-staining with antibodies to XPC, the initial UV-induced DNA damage recognition sensor, revealed that XPC rapidly accumulated at DNA damage foci and gradually faded over 90 minu...
Source: Journal of Investigative Dermatology - June 17, 2020 Category: Dermatology Authors: C. Wong, D.H. Oh Tags: Photobiology Source Type: research

Role of Mitogen activated-kinase (MAPK)-phosphatase (MKP)-5 in pulmonary fibrosis
Conclusion: Intact MKP5 is required for induction of changes in lung fibroblasts in-vitro and during bleomycin-induced lung fibrosis in-vivo. MKP5 inhibition represent a promising therapeutic target for experimental and lung fibrosis.
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Tzouvelekis, A., Karampitsakos, T., Min, K., Xylourgidis, N., Yu, G., Herazo-Maya, J., Bizenhofer, L., Bennett, A., Kaminski, N. Tags: Idiopathic interstitial pneumonias Source Type: research

MKP-5 inhibition blunts fibrotic responses in-vitro and in-vivo through negative regulation of TGFB1-induced smad3-signalling
Conclusion: We conclude that intact MKP5 is required for induction of changes in lung fibroblasts in-vitro and during bleomycin-induced lung fibrosis in-vivo. Our results couple MKP5 activity with TGFB1 signaling machinery identifying MKP5 inhibition as a promising therapeutic strategy for experimental and human lung fibrosis.
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Tzouvelekis, A., Xylourgidis, N., Min, K., Karampitsakos, T., Ninou, I., Barbayianni, I., Bennett, A., Aidinis, V., Kaminski, N. Tags: Mechanisms of Lung Injury and Repair Source Type: research

1173 Inducible DNA repair of UV photoproducts depends on vitamin D receptor
Ultraviolet radiation (UV) initiates vitamin D synthesis by converting 7-dehydrocholesterol to pre-vitamin D3 that is converted to 25-hydroxyvitamin D3 (25D3) and then 1,25-dihydroxyvitamin D3 (1,25D3). However, UV also generates DNA damage that is repaired by nucleotide excision repair (NER). We tested the hypothesis that vitamin D signaling elicits compensatory responses to the DNA damage incurred during vitamin D synthesis. Treatment of human keratinocytes with either UVB or with 1,25D3 or 25D3 induced the DNA damage recognition protein, XPC, and induction was suppressed by either siRNA targeting the vitamin D receptor ...
Source: Journal of Investigative Dermatology - April 27, 2018 Category: Dermatology Authors: A. Scandurra, C. Wong, T. Kaur Oberoi, D. Oh Tags: Photobiology Source Type: research

Identification of vitamin B1 metabolism as a tumor-specific radiosensitizing pathway using a high-throughput colony formation screen.
Authors: Tiwana GS, Prevo R, Buffa FM, Yu S, Ebner DV, Howarth A, Folkes LK, Budwal B, Chu KY, Durrant L, Muschel RJ, McKenna WG, Higgins GS Abstract Colony formation is the gold standard assay for determining reproductive cell death after radiation treatment, since effects on proliferation often do not reflect survival. We have developed a high-throughput radiosensitivity screening method based on clonogenicity and screened a siRNA library against kinases. Thiamine pyrophosphokinase-1 (TPK1), a key component of Vitamin B1/thiamine metabolism, was identified as a target for radiosensitization. TPK1 knockdown caused...
Source: Oncotarget - March 22, 2015 Category: Cancer & Oncology Tags: Oncotarget Source Type: research