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The DNA damage response activates HPV16 late gene expression at the level of RNA processing

Nilsson, Kersti LU ; Wu, Chengjun LU ; Kajitani, Naoko LU ; Yu, Haoran LU ; Tsimtsirakis, Efthymios LU ; Gong, Lijing LU ; Winquist, Ellenor B. LU ; Glahder, Jacob LU ; Ekblad, Lars LU and Wennerberg, Johan LU , et al. (2018) In Nucleic Acids Research 46(10). p.5029-5049
Abstract

We show that the alkylating cancer drug melphalan activated the DNA damage response and induced human papillomavirus type 16 (HPV16) late gene expression in an ATM- and Chk1/2-dependent manner. Activation of HPV16 late gene expression included inhibition of the HPV16 early polyadenylation signal that resulted in read-through into the late region of HPV16. This was followed by activation of the exclusively late, HPV16 splice sites SD3632 and SA5639 and production of spliced late L1 mRNAs. Altered HPV16 mRNA processing was paralleled by increased association of phosphorylated BRCA1, BARD1, BCLAF1 and TRAP150 with HPV16 DNA, and increased association of RNA processing factors U2AF65 and hnRNP C with HPV16 mRNAs. These RNA processing... (More)

We show that the alkylating cancer drug melphalan activated the DNA damage response and induced human papillomavirus type 16 (HPV16) late gene expression in an ATM- and Chk1/2-dependent manner. Activation of HPV16 late gene expression included inhibition of the HPV16 early polyadenylation signal that resulted in read-through into the late region of HPV16. This was followed by activation of the exclusively late, HPV16 splice sites SD3632 and SA5639 and production of spliced late L1 mRNAs. Altered HPV16 mRNA processing was paralleled by increased association of phosphorylated BRCA1, BARD1, BCLAF1 and TRAP150 with HPV16 DNA, and increased association of RNA processing factors U2AF65 and hnRNP C with HPV16 mRNAs. These RNA processing factors inhibited HPV16 early polyadenylation and enhanced HPV16 late mRNA splicing, thereby activating HPV16 late gene expression.

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published
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Nucleic Acids Research
volume
46
issue
10
pages
5029 - 5049
publisher
Oxford University Press
external identifiers
  • scopus:85048558077
  • pmid:29596642
ISSN
0305-1048
DOI
10.1093/nar/gky227
language
English
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yes
id
53ea22ed-fdb1-41b9-8789-0048ec38f30a
date added to LUP
2019-10-17 12:57:01
date last changed
2020-03-24 07:04:48
@article{53ea22ed-fdb1-41b9-8789-0048ec38f30a,
  abstract     = {<p>We show that the alkylating cancer drug melphalan activated the DNA damage response and induced human papillomavirus type 16 (HPV16) late gene expression in an ATM- and Chk1/2-dependent manner. Activation of HPV16 late gene expression included inhibition of the HPV16 early polyadenylation signal that resulted in read-through into the late region of HPV16. This was followed by activation of the exclusively late, HPV16 splice sites SD3632 and SA5639 and production of spliced late L1 mRNAs. Altered HPV16 mRNA processing was paralleled by increased association of phosphorylated BRCA1, BARD1, BCLAF1 and TRAP150 with HPV16 DNA, and increased association of RNA processing factors U2AF65 and hnRNP C with HPV16 mRNAs. These RNA processing factors inhibited HPV16 early polyadenylation and enhanced HPV16 late mRNA splicing, thereby activating HPV16 late gene expression.</p>},
  author       = {Nilsson, Kersti and Wu, Chengjun and Kajitani, Naoko and Yu, Haoran and Tsimtsirakis, Efthymios and Gong, Lijing and Winquist, Ellenor B. and Glahder, Jacob and Ekblad, Lars and Wennerberg, Johan and Schwartz, Stefan},
  issn         = {0305-1048},
  language     = {eng},
  month        = {01},
  number       = {10},
  pages        = {5029--5049},
  publisher    = {Oxford University Press},
  series       = {Nucleic Acids Research},
  title        = {The DNA damage response activates HPV16 late gene expression at the level of RNA processing},
  url          = {http://dx.doi.org/10.1093/nar/gky227},
  doi          = {10.1093/nar/gky227},
  volume       = {46},
  year         = {2018},
}