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Article

UVA-induced upregulation of progerin suppresses 53BP1‑mediated NHEJ DSB repair in human keratinocytes via progerin-lamin A complex formation

  • Authors:
    • Xin Huang
    • Yun Pan
    • Di Cao
    • Sheng Fang
    • Kun Huang
    • Jin Chen
    • Aijun Chen
  • View Affiliations / Copyright

    Affiliations: Prescriptions Department, College of Traditional Chinese Medicine, Chongqing Medical University, Yuzhong, Chongqing, P.R. China, Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing, P.R. China
  • Pages: 3617-3624
    |
    Published online on: April 26, 2017
       https://doi.org/10.3892/or.2017.5603
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Abstract

Ultraviolet (UV) radiation is the primary risk factor underlying photoaging and photocarcinogenesis. Mounting research has focused on the role of DNA damage response pathways in UV-induced double-strand break (DSB) repair. In the present study, we hypothesized that UVA-induced aberrant progerin upregulation may adversely affect p53-binding protein 1 (53BP1)-mediated non-homologous end joining (NHE) DSB repair in human keratinocytes. Basal cell carcinoma (BCC) tumors and matching normal skin tissue were sampled (n=200) to investigate whether human keratinocytes display dysregulated progerin expression as a function of advancing age and BCC status. Newborn foreskin samples (n=9) were used as a source for primary keratinocyte cultures. We investigated the effects of UVA radiation on progerin and lamin A expression as well as the effects of the silencing of progerin on lamin A protein expression in UVA-irradiated keratinocytes. We investigated whether blocking progerin‑lamin A interaction was able to rescue UVA-induced lamin A protein downregulation, 53BP1 downregulation and 53BP1-mediated NHEJ DSB repair activity. Progerin upregulation in adult keratinocytes was associated with advancing age, not BCC status. In vitro, UVA exposure significantly upregulated progerin expression by favoring alternative LMNA gene transcript splicing. UVA exposure significantly downregulated free (unbound) lamin A protein levels via progerin-lamin A complex formation. UVA exposure significantly decreased 53BP1 protein levels via enhanced progerin-lamin A complex formation. UVA-induced progerin‑lamin A complex formation was largely responsible for suppressing 53BP1-mediated NHEJ DSB repair activity. The present study is the first to demonstrate that UVA-induced progerin upregulation adversely affects 53BP1-mediated NHEJ DSB repair in human keratinocytes via progerin‑lamin A complex formation.
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1 

Moan J, Grigalavicius M, Baturaite Z, Dahlback A and Juzeniene A: The relationship between UV exposure and incidence of skin cancer. Photodermatol Photoimmunol Photomed. 31:26–35. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Iannacone MR, Hughes MCB and Green AC: Effects of sunscreen on skin cancer and photoaging. Photodermatol Photoimmunol Photomed. 30:55–61. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Kabir Y, Seidel R, Mcknight B and Moy R: DNA repair enzymes: An important role in skin cancer prevention and reversal of photodamage - a review of the literature. J Drugs Dermatol. 14:297–303. 2015.PubMed/NCBI

4 

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI

5 

Schwertman P, Bekker-Jensen S and Mailand N: Regulation of DNA double-strand break repair by ubiquitin and ubiquitin-like modifiers. Nat Rev Mol Cell Biol. 17:379–394. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Surovtseva Y, Jairam V, Sundaram R, Bindra R and Herzon S: A high-throughput, high-content assay for the discovery of new inhibitors of DNA double-strand break repair. Cancer Res. 76(Suppl 14): 21742016.doi: 10.1158/1538-7445.AM2016-2174. View Article : Google Scholar

7 

Gibbs-Seymour I, Markiewicz E, Bekker-Jensen S, Mailand N and Hutchison CJ: Lamin A/C-dependent interaction with 53BP1 promotes cellular responses to DNA damage. Aging Cell. 14:162–169. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Canny M, Wan L, Fradet-Turcotte A, Orthwein A, Moatti N, Juang YC, Zhang W, Noordermeer SM, Wilson MD, Vorobyov A, et al: A genetically encoded inhibitor of 53BP1 to 1 stimulate homology-based gene editing. bioRxiv. 0609542016.https://doi.org/10.1101/060954

9 

Her SC and Her C: Targeting DNA double-strand break repair in cancer therapy. J Mol Genet Med. 9:e1062015.

10 

Redwood AB, Perkins SM, Vanderwaal RP, Feng Z, Biehl KJ, Gonzalez-Suarez I, Morgado-Palacin L, Shi W, Sage J, Roti-Roti JL, et al: A dual role for A-type lamins in DNA double-strand break repair. Cell Cycle. 10:2549–2560. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Takeuchi H and Rünger TM: Longwave UV light induces the aging-associated progerin. J Invest Dermatol. 133:1857–1862. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Lee SJ, Jung YS, Yoon MH, Kang SM, Oh AY, Lee JH, Jun SY, Woo TG, Chun HY, Kim SK, et al: Interruption of progerin-lamin A/C binding ameliorates Hutchinson-Gilford progeria syndrome phenotype. J Clin Invest. 126:3879–3893. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Waldman AS, Chowdhary S, Patrick A, Hersey M and Waldman BC: The influence of progerin expression on the nature of DNA double-strand break repair. The FASEB J. 30:(Suppl 1): S576.42016.

14 

Mistry DS, Chen Y, Wang Y and Sen GL: Transcriptional profiling of SNAI2 regulated genes in primary human keratinocytes. Genom Data. 4:43–46. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Malaisse J, Pendaries V, Hontoir F, De Glas V, van Vlaender D, Simon M, de Rouvroit C Lambert, Poumay Y and Flamion B: Hyaluronan does not regulate human epidermal keratinocyte proliferation and differentiation. J Biol Chem. 291:6347–6358. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Zhang H, Xiong Z-M and Cao K: Mechanisms controlling the smooth muscle cell death in progeria via down-regulation of poly(ADP-ribose) polymerase 1. Proc Natl Acad Sci USA. 111:pp. E2261–E2270. 2014; View Article : Google Scholar : PubMed/NCBI

17 

Woods M, Pant R and Mallya SM: Cyclin D1 and cyclin D-dependent kinases enhance oral keratinocyte proliferation but do not block keratinocyte differentiation. Int J Oncol. 37:1471–1475. 2010.PubMed/NCBI

18 

Musich PR and Zou Y: DNA-damage accumulation and replicative arrest in Hutchinson-Gilford progeria syndrome. Biochem Soc Trans. 39:1764–1769. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Miller JD, Ganat YM, Kishinevsky S, Bowman RL, Liu B, Tu EY, Mandal PK, Vera E, Shim JW, Kriks S, et al: Human iPSC-based modeling of late-onset disease via progerin-induced aging. Cell Stem Cell. 13:691–705. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Kubben N, Zhang W, Wang L, Voss TC, Yang J, Qu J, Liu GH and Misteli T: Repression of the antioxidant NRF2 pathway in premature aging. Cell. 165:1361–1374. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Kennedy BK: A new connection between VHL and cancer threads through progerin. Cell Cycle. 12:2721–2722. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Olive M, Harten I, Mitchell R, Beers JK, Djabali K, Cao K, Erdos MR, Blair C, Funke B, Smoot L, et al: Cardiovascular pathology in Hutchinson-Gilford progeria: Correlation with the vascular pathology of aging. Arterioscler Thromb Vasc Biol. 30:2301–2309. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Firoozan S, Takeuchi H and Ruenger T: Longwave ultraviolet light induces the aging-associated progerin in melanocytes. Am J Med Genet. 2603:26242006.

24 

Gonzalez-Suarez I, Redwood AB, Grotsky DA, Neumann MA, Cheng EHY, Stewart CL, Dusso A and Gonzalo S: A new pathway that regulates 53BP1 stability implicates cathepsin L and vitamin D in DNA repair. EMBO J. 30:3383–3396. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Ghosh S, Liu B, Wang Y, Hao Q and Zhou Z: Lamin A is an endogenous SIRT6 activator and promotes SIRT6-mediated DNA repair. Cell Reports. 13:1396–1406. 2015. View Article : Google Scholar : PubMed/NCBI

26 

Mao Z, Hine C, Tian X, van Meter M, Au M, Vaidya A, Seluanov A and Gorbunova V: SIRT6 promotes DNA repair under stress by activating PARP1. Science. 332:1443–1446. 2011. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Huang X, Pan Y, Cao D, Fang S, Huang K, Chen J and Chen A: UVA-induced upregulation of progerin suppresses 53BP1‑mediated NHEJ DSB repair in human keratinocytes via progerin-lamin A complex formation. Oncol Rep 37: 3617-3624, 2017.
APA
Huang, X., Pan, Y., Cao, D., Fang, S., Huang, K., Chen, J., & Chen, A. (2017). UVA-induced upregulation of progerin suppresses 53BP1‑mediated NHEJ DSB repair in human keratinocytes via progerin-lamin A complex formation. Oncology Reports, 37, 3617-3624. https://doi.org/10.3892/or.2017.5603
MLA
Huang, X., Pan, Y., Cao, D., Fang, S., Huang, K., Chen, J., Chen, A."UVA-induced upregulation of progerin suppresses 53BP1‑mediated NHEJ DSB repair in human keratinocytes via progerin-lamin A complex formation". Oncology Reports 37.6 (2017): 3617-3624.
Chicago
Huang, X., Pan, Y., Cao, D., Fang, S., Huang, K., Chen, J., Chen, A."UVA-induced upregulation of progerin suppresses 53BP1‑mediated NHEJ DSB repair in human keratinocytes via progerin-lamin A complex formation". Oncology Reports 37, no. 6 (2017): 3617-3624. https://doi.org/10.3892/or.2017.5603
Copy and paste a formatted citation
x
Spandidos Publications style
Huang X, Pan Y, Cao D, Fang S, Huang K, Chen J and Chen A: UVA-induced upregulation of progerin suppresses 53BP1‑mediated NHEJ DSB repair in human keratinocytes via progerin-lamin A complex formation. Oncol Rep 37: 3617-3624, 2017.
APA
Huang, X., Pan, Y., Cao, D., Fang, S., Huang, K., Chen, J., & Chen, A. (2017). UVA-induced upregulation of progerin suppresses 53BP1‑mediated NHEJ DSB repair in human keratinocytes via progerin-lamin A complex formation. Oncology Reports, 37, 3617-3624. https://doi.org/10.3892/or.2017.5603
MLA
Huang, X., Pan, Y., Cao, D., Fang, S., Huang, K., Chen, J., Chen, A."UVA-induced upregulation of progerin suppresses 53BP1‑mediated NHEJ DSB repair in human keratinocytes via progerin-lamin A complex formation". Oncology Reports 37.6 (2017): 3617-3624.
Chicago
Huang, X., Pan, Y., Cao, D., Fang, S., Huang, K., Chen, J., Chen, A."UVA-induced upregulation of progerin suppresses 53BP1‑mediated NHEJ DSB repair in human keratinocytes via progerin-lamin A complex formation". Oncology Reports 37, no. 6 (2017): 3617-3624. https://doi.org/10.3892/or.2017.5603
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