Absence of Non-histone Protein Complexes at Natural Chromosomal Pause Sites Results in Reduced Replication Pausing in Aging Yeast Cells.
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.
Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Rutgers Biomedical and Health Sciences, 185 South Orange Avenue, Newark, NJ 07101-1709, USA.
Marleny
M
Cabral
Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Rutgers Biomedical and Health Sciences, 185 South Orange Avenue, Newark, NJ 07101-1709, USA.
Xin
X
Cheng
Pathology and Laboratory Medicine/Flow Cytometry and Immunology Core Laboratory, Rutgers New Jersey Medical School, Rutgers Biomedical and Health Sciences, 185 South Orange Avenue, Newark, NJ 07101-1709, USA.
Sukhwinder
S
Singh
Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Rutgers Biomedical and Health Sciences, 185 South Orange Avenue, Newark, NJ 07101-1709, USA. Electronic address: ivessaan@njms.rutgers.edu.
Andreas S
AS
Ivessa
D002467:Cell Nucleus / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D015825:Chromosomes, Fungal / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004261:DNA Replication; D004275:DNA, Ribosomal / Q000235:genetics; D005800:Genes, Fungal; D046912:Multiprotein Complexes / Q000378:metabolism*; D051738:Origin Recognition Complex / Q000378:metabolism; D018741:Replication Origin / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; D004275:DNA, Ribosomal; D046912:Multiprotein Complexes; D051738:Origin Recognition Complex; D029701:Saccharomyces cerevisiae Proteins
DNA damage; DNA replication; aging; baker's yeast; chromosomal DNA; chromosomal fragile sites; non-histone protein complexes; replicative aging