Format

Send to

Choose Destination
Mol Cell. 2009 Sep 11;35(5):683-93. doi: 10.1016/j.molcel.2009.07.012.

The effect of replication initiation on gene amplification in the rDNA and its relationship to aging.

Author information

1
National Institute of Genetics, Sokendai-Mishima, Japan.

Abstract

In eukaryotes, the ribosomal DNA (rDNA) consists of long tandem repeat arrays. These repeated genes are unstable because homologous recombination between them results in copy number loss. To maintain high copy numbers, yeast has an amplification system that works through a pathway involving the replication fork barrier site and unequal sister chromatid recombination. In this study, we show that an active replication origin is essential for amplification, and the amplification rate correlates with origin activity. Moreover, origin activity affects the levels of extrachromosomal rDNA circles (ERC) that are thought to promote aging. Surprisingly, we found that reduction in ERC level results in shorter life span. We instead show that life span correlates with rDNA stability, which is preferentially reduced in mother cells, and that episomes can induce rDNA instability. These data support a model in which rDNA instability itself is a cause of aging in yeast.

PMID:
19748361
DOI:
10.1016/j.molcel.2009.07.012
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center