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Nucleotide excision repair capacity increases during differentiation of human embryonic carcinoma cells into neurons and muscle cells

Li, Wentao and Liu, Wenjie and Kakoki, Ayano and Wang, Rujin and Adebali, Ogün and Jiang, Yuchao and Sancar, Aziz (2019) Nucleotide excision repair capacity increases during differentiation of human embryonic carcinoma cells into neurons and muscle cells. Journal of Biological Chemistry, 294 (15). pp. 5914-5922. ISSN 0021-9258 (Print) 1083-351X (Online)

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Official URL: http://dx.doi.org/10.1074/jbc.RA119.007861

Abstract

Embryonic stem cells can self-renew and differentiate, holding great promise for regenerative medicine. They also employ multiple mechanisms to preserve the integrity of their genomes. Nucleotide excision repair, a versatile repair mechanism, removes bulky DNA adducts from the genome. However, the dynamics of the capacity of nucleotide excision repair during stem cell differentiation remain unclear. Here, using immunoslot blot assay, we measured repair rates of UV-induced DNA damage during differentiation of human embryonic carcinoma (NTERA-2) cells into neurons and muscle cells. Our results revealed that the capacity of nucleotide excision repair increases as cell differentiation progresses. We also found that inhibition of the apoptotic signaling pathway has no effect on nucleotide excision repair capacity. Furthermore, RNA-Seq-based transcriptomic analysis indicated that expression levels of four core repair factors, xeroderma pigmentosum (XP) complementation group A (XPA), XPC, XPG, and XPF-ERCC1, are progressively up-regulated during differentiation, but not those of replication protein A (RPA) and transcription factor IIH (TFIIH). Together, our findings reveal that increase of nucleotide excision repair capacity accompanies cell differentiation, supported by the up-regulated transcription of genes encoding DNA repair enzymes during differentiation of two distinct cell lineages.

Item Type:Article
Uncontrolled Keywords:nucleotide excision repair; cancer stem cells; differentiation; neuron; vascular smooth muscle cells; muscle cell; neuron; nucleotide excision repair; stem cell; cell differentiation; genome stability; transcriptomics; NT2 cell; retinoic acid (RA); bone morphogenetic protein-2 (BMP-2)
Subjects:Q Science > Q Science (General)
ID Code:37196
Deposited By:Ogün Adebali
Deposited On:23 Aug 2019 15:29
Last Modified:23 Aug 2019 15:29

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