title: Transcriptional and post-transcriptional regulation of nucleotide excision repair genes in human cells.
abstract: Nucleotide excision repair (NER) removes DNA helix-distorting lesions induced by UV light and various chemotherapeutic agents such as cisplatin. These lesions efficiently block the elongation of transcription and need to be rapidly removed by transcription-coupled NER (TC-NER) to avoid the induction of apoptosis. Twenty-nine genes have been classified to code for proteins participating in nucleotide excision repair (NER) in human cells. Here we explored the transcriptional and post-transcriptional regulation of these NER genes across 13 human cell lines using Bru-seq and BruChase-seq, respectively. Many NER genes are relatively large in size and therefore will be easily inactivated by UV-induced transcription-blocking lesions. Furthermore, many of these genes produce transcripts that are rather unstable. Thus, these genes are expected to rapidly lose expression leading to a diminished function of NER. One such gene is ERCC6 that codes for the CSB protein critical for TC-NER. Due to its large gene size and high RNA turnover rate, the ERCC6 gene may act as dosimeter of DNA damage so that at high levels of damage, ERCC6 RNA levels would be diminished leading to the loss of CSB expression, inhibition of TC-NER and the promotion of cell death.
authors.affiliation: Translational Oncology Program, University of Michigan Medical School, Ann Arbor, MI, United States.
authors.forename: Hailey B
authors.initials: HB
authors.lastname: Lefkofsky
authors.affiliation: Translational Oncology Program, University of Michigan Medical School, Ann Arbor, MI, United States; Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, United States; Bioinformatics Program, Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Artur
authors.initials: A
authors.lastname: Veloso
authors.affiliation: Translational Oncology Program, University of Michigan Medical School, Ann Arbor, MI, United States; Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, United States; Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, United States. Electronic address: ljungman@umich.edu.
authors.forename: Mats
authors.initials: M
authors.lastname: Ljungman
mesh_terms: D004265:DNA Helicases / Q000096:biosynthesis*; D004260:DNA Repair / Q000502:physiology* / Q000528:radiation effects; D045643:DNA Repair Enzymes / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology* / Q000528:radiation effects; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D000075223:Poly-ADP-Ribose Binding Proteins; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic / Q000502:physiology* / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D000075223:Poly-ADP-Ribose Binding Proteins; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes
keywords: DNA repair; RNA stability; Transcription