Transcriptional and post-transcriptional regulation of nucleotide excision repair
genes in human cells
#MMPMID26255935
Lefkofsky HB
; Veloso A
; Ljungman M
Mutat Res
2015[Jun]; 776
(?): 9-15
PMID26255935
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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.
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