PARP1 promoter links cell cycle progression with adaptation to oxidative environment

Julita Pietrzak, Corinne M. Spickett, Tomasz Płoszaj, László Virág, Agnieszka Robaszkiewicz

Research output: Contribution to journalReview article

12 Citations (Scopus)

Abstract

Although electrophiles are considered as detrimental to cells, accumulating recent evidence indicates that proliferating non-cancerous and particularly cancerous cells utilize these agents for pro-survival and cell cycle promoting signaling. Hence, the redox shift to mild oxidant release must be balanced by multiple defense mechanisms. Our latest findings demonstrate that cell cycle progression, which dictates oxidant level in stress-free conditions, determines PARP1 transcription. Growth modulating factors regulate CDK4/6-RBs-E2Fs axis. In cells arrested in G1 and G0, RB1-E2F1 and RBL2-E2F4 dimers recruit chromatin remodelers such as HDAC1, SWI/SNF and PRC2 to condense chromatin and turn off transcription. Release of retinoblastoma-based repressive complexes from E2F-dependent gene promoters in response to cell transition to S phase enables transcription of PARP1. This enzyme contributes to repair of oxidative DNA damage by supporting several strand break repair pathways and nucleotide or base excision repair pathways, as well as acting as a co-activator of transcription factors such as NRF2 and HIF1a, which control expression of antioxidant enzymes involved in removal of electrophiles and secondary metabolites. Furthermore, PARP1 is indispensible for transcription of the pro-survival kinases MAP2K6, ERK1/2 and AKT1, and for maintaining MAPK activity by suppressing transcription of the MAPK inhibitor, MPK1. In summary, cell cycle controlled PARP1 transcription helps cells to adapt to a pro-oxidant redox shift.

Original languageEnglish
Pages (from-to)1-5
Number of pages5
JournalRedox Biology
Volume18
DOIs
Publication statusPublished - Sep 2018

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Keywords

  • Cell proliferation
  • DNA repair
  • Gene transcription
  • Poly-ADP-ribose polymerase 1 (PARP1)
  • Redox homeostasis
  • Signaling

ASJC Scopus subject areas

  • Organic Chemistry
  • Clinical Biochemistry

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