Acidic growth conditions stabilize the ribosomal RNA gene cluster and extend lifespan through noncoding transcription repression

Author:

Hasegawa Yo12,Ooka Hiroyuki12,Wakatsuki Tsuyoshi123,Sasaki Mariko1,Yamamoto Ayumi4,Kobayashi Takehiko1235ORCID

Affiliation:

1. Laboratory of Genome Regeneration Institute for Quantitative Biosciences (IQB) The University of Tokyo Bunkyo‐ku Japan

2. Department of Biological Sciences, Graduate School of Science The University of Tokyo Bunkyo‐ku Japan

3. Department of Life Science and Technology Tokyo Institute of Technology Midori‐ku Japan

4. Department of Industrial System Engineering Hachinohe College Hachinohe Japan

5. Collaborative Research Institute for Innovative Microbiology The University of Tokyo Bunkyo‐ku Japan

Abstract

AbstractBlackcurrant (Ribes nigrum L.) is a classical fruit that has long been used to make juice, jam, and liqueur. Blackcurrant extract is known to relieve cells from DNA damage caused by hydrogen peroxide (H2O2), methyl methane sulfonate (MMS), and ultraviolet (UV) radiation. We found that blackcurrant extract (BCE) stabilizes the ribosomal RNA gene cluster (rDNA), one of the most unstable regions in the genome, through repression of noncoding transcription in the intergenic spacer (IGS) which extended the lifespan in budding yeast. Reduced formation of extrachromosomal circles (ERCs) after exposure to fractionated BCE suggested that acidity of the growth medium impacted rDNA stability. Indeed, alteration of the acidity of the growth medium to pH ~4.5 by adding HCl increased rDNA stability and extended the lifespan. We identified RPD3 as the gene responsible for this change, which was mediated by the RPD3L histone deacetylase complex. In mammals, as inflammation sites in a tissue are acidic, DNA maintenance may be similarly regulated to prevent genome instability from causing cancer.

Funder

Japan Society for the Promotion of Science

Publisher

Wiley

Subject

Cell Biology,Genetics

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