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

TitleNucleotide excision repair capacity increases during differentiation of human embryonic carcinoma cells into neurons and muscle cells.
Publication TypeJournal Article
Year of Publication2019
AuthorsLi, Wentao, Wenjie Liu, Ayano Kakoki, Rujin Wang, Ogun Adebali, Yuchao Jiang, and Aziz Sancar
JournalJ Biol Chem
Volume294
Issue15
Pagination5914-5922
Date Published2019 04 12
ISSN1083-351X
KeywordsCell Differentiation, Cell Line, Tumor, DNA Repair, DNA-Binding Proteins, Embryonal Carcinoma Stem Cells, Endonucleases, Humans, Muscle Cells, Neoplasm Proteins, Neurons, Nuclear Proteins, Replication Protein A, Transcription Factor TFIIH, Transcription Factors, Xeroderma Pigmentosum Group A Protein
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.

DOI10.1074/jbc.RA119.007861
Alternate JournalJ Biol Chem
Original PublicationNucleotide excision repair capacity increases during differentiation of human embryonic carcinoma cells into neurons and muscle cells.
PubMed ID30808711
PubMed Central IDPMC6463700
Grant ListP01 CA142538 / CA / NCI NIH HHS / United States
P30 ES010126 / ES / NIEHS NIH HHS / United States
R01 ES027255 / ES / NIEHS NIH HHS / United States
R35 GM118102 / GM / NIGMS NIH HHS / United States