Absence of Non-histone Protein Complexes at Natural Chromosomal Pause Sites Results in Reduced Replication Pausing in Aging Yeast Cells

Marleny Cabral, Xin Cheng, Sukhwinder Singh, Andreas S. Ivessa

Research output: Contribution to journalArticle

4 Scopus citations

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 languageEnglish (US)
Pages (from-to)1747-1754
Number of pages8
JournalCell Reports
Volume17
Issue number7
DOIs
StatePublished - Nov 8 2016

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Keywords

  • DNA damage
  • DNA replication
  • aging
  • baker's yeast
  • chromosomal DNA
  • chromosomal fragile sites
  • non-histone protein complexes
  • replicative aging

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