Nucleosome remodelling, DNA repair and transcriptional regulation build negative feedback loops in cancer and cellular ageing

Reiko Watanabe, Shin Ichiro Kanno, Amaneh Mohammadi Roushandeh, Ayako Ui, Akira Yasui

Research output: Contribution to journalReview article

10 Citations (Scopus)

Abstract

Nucleosome remodelling (NR) regulates transcription in an ATP-dependent manner, and influences gene expression required for development and cellular functions, including those involved in anti-cancer and anti-ageing processes. ATP-utilizing chromatin assembly and remodelling factor (ACF) and Brahma-associated factor (BAF) complexes, belonging to the ISWI and SWI/ SNF families, respectively, are involved in various types of DNA repair. Suppression of several BAF factors makes U2OS cells significantly sensitive to X-rays, UV and especially to cisplatin, and these BAF factors contribute to the accumulation of repair proteins at various types of DNA damage and to DNA repair. Recent cancer genome sequencing and expression analysis has shown that BAF factors are frequently mutated or, more frequently, silenced in various types of cancer cells. Thus, those cancer cells are potentially X-ray-and especially cisplatin-sensitive, suggesting a way of optimizing current cancer therapy. Recent single–stem cell analysis suggests that mutations and epigenetic changes influence stem cell functionality leading to cellular ageing. Genetic and epigenetic changes in the BAF factors diminish DNA repair as well as transcriptional regulation activities, and DNA repair defects in turn negatively influence NR and transcriptional regulation. Thus, they build negative feedback loops, which accelerate both cellular senescence and transformation as common and rare cellular events, respectively, causing cellular ageing.

Original languageEnglish
Article number20160473
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Volume372
Issue number1731
DOIs
Publication statusPublished - 2017 Jan 1

Keywords

  • BAF complex
  • Cancer therapy
  • Cellular aging
  • Chromatin remodeling
  • DNA repair
  • Nucleosome remodeling

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Fingerprint Dive into the research topics of 'Nucleosome remodelling, DNA repair and transcriptional regulation build negative feedback loops in cancer and cellular ageing'. Together they form a unique fingerprint.

  • Cite this