Abstract
There is substantial evidence that genomic instability increases during aging. Replication pausing (and stalling) at difficult-to-replicate chromosomal sites may induce genomic instability. Interestingly, in aging yeast cells, we observed reduced replication pausing at various natural replication pause sites (RPSs) in ribosomal DNA (rDNA) and non-rDNA locations (e.g., silent replication origins and tRNA genes). The reduced pausing occurs independent of the DNA helicase Rrm3p, which facilitates replication past these non-histone protein-complex-bound RPSs, and is independent of the deacetylase Sir2p. Conditions of caloric restriction (CR), which extend life span, also cause reduced replication pausing at the 5S rDNA and at tRNA genes. In aged and CR cells, the RPSs are less occupied by their specific non-histone protein complexes (e.g., the preinitiation complex TFIIIC), likely because members of these complexes have primarily cytosolic localization. These conditions may lead to reduced replication pausing and may lower replication stress at these sites during aging.
| Original language | American English |
|---|---|
| Pages (from-to) | 1747-1754 |
| Number of pages | 8 |
| Journal | Cell Reports |
| Volume | 17 |
| Issue number | 7 |
| DOIs | |
| State | Published - Nov 8 2016 |
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
Keywords
- DNA damage
- DNA replication
- aging
- baker's yeast
- chromosomal DNA
- chromosomal fragile sites
- non-histone protein complexes
- replicative aging