Biomaterial Database

Extrachromosomal rDNA circles--a cause of aging in yeast. 1997

D A Sinclair, and L Guarente

Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.

Although many cellular and organismal changes have been described in aging individuals, a precise, molecular cause of aging has yet to be found. A prior study of aging yeast mother cells showed a progressive enlargement and fragmentation of the nucleolus. Here we show that these nucleolar changes are likely due to the accumulation of extrachromosomal rDNA circles (ERCs) in old cells and that, in fact, ERCs cause aging. Mutants for sgs1, the yeast homolog of the Werner's syndrome gene, accumulate ERCs more rapidly, leading to premature aging and a shorter life span. We speculate on the generality of this molecular cause of aging in higher species, including mammals.

UI	MeSH Term	Description	Entries
D002466	Cell Nucleolus	Within most types of eukaryotic CELL NUCLEUS, a distinct region, not delimited by a membrane, in which some species of rRNA (RNA, RIBOSOMAL) are synthesized and assembled into ribonucleoprotein subunits of ribosomes. In the nucleolus rRNA is transcribed from a nucleolar organizer, i.e., a group of tandemly repeated chromosomal genes which encode rRNA and which are transcribed by RNA polymerase I. (Singleton & Sainsbury, Dictionary of Microbiology & Molecular Biology, 2d ed)	Plasmosome,Cell Nucleoli,Nucleoli, Cell,Nucleolus, Cell,Plasmosomes
D004265	DNA Helicases	Proteins that catalyze the unwinding of duplex DNA during replication by binding cooperatively to single-stranded regions of DNA or to short regions of duplex DNA that are undergoing transient opening. In addition, DNA helicases are DNA-dependent ATPases that harness the free energy of ATP hydrolysis to translocate DNA strands.	ATP-Dependent DNA Helicase,DNA Helicase,DNA Unwinding Protein,DNA Unwinding Proteins,ATP-Dependent DNA Helicases,DNA Helicase A,DNA Helicase E,DNA Helicase II,DNA Helicase III,ATP Dependent DNA Helicase,ATP Dependent DNA Helicases,DNA Helicase, ATP-Dependent,DNA Helicases, ATP-Dependent,Helicase, ATP-Dependent DNA,Helicase, DNA,Helicases, ATP-Dependent DNA,Helicases, DNA,Protein, DNA Unwinding,Unwinding Protein, DNA,Unwinding Proteins, DNA
D004270	DNA, Circular	Any of the covalently closed DNA molecules found in bacteria, many viruses, mitochondria, plastids, and plasmids. Small, polydisperse circular DNA's have also been observed in a number of eukaryotic organisms and are suggested to have homology with chromosomal DNA and the capacity to be inserted into, and excised from, chromosomal DNA. It is a fragment of DNA formed by a process of looping out and deletion, containing a constant region of the mu heavy chain and the 3'-part of the mu switch region. Circular DNA is a normal product of rearrangement among gene segments encoding the variable regions of immunoglobulin light and heavy chains, as well as the T-cell receptor. (Riger et al., Glossary of Genetics, 5th ed & Segen, Dictionary of Modern Medicine, 1992)	Circular DNA,Circular DNAs,DNAs, Circular
D004271	DNA, Fungal	Deoxyribonucleic acid that makes up the genetic material of fungi.	Fungal DNA
D004275	DNA, Ribosomal	DNA sequences encoding RIBOSOMAL RNA and the segments of DNA separating the individual ribosomal RNA genes, referred to as RIBOSOMAL SPACER DNA.	Ribosomal DNA,rDNA
D000375	Aging	The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.	Senescence,Aging, Biological,Biological Aging
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor
D015003	Yeasts	A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are SACCHAROMYCES CEREVISIAE; therapeutic dried yeast is YEAST, DRIED.	Yeast
D016922	Cellular Senescence	Process by which cells irreversibly stop dividing and enter a state of permanent growth arrest without undergoing CELL DEATH. Senescence can be induced by DNA DAMAGE or other cellular stresses, such as OXIDATIVE STRESS.	Aging, Cell,Cell Aging,Cell Senescence,Replicative Senescence,Senescence, Cellular,Senescence, Replicative,Cell Ageing,Cellular Ageing,Cellular Aging,Ageing, Cell,Ageing, Cellular,Aging, Cellular,Senescence, Cell
D053484	RecQ Helicases	A family of structurally-related DNA helicases that play an essential role in the maintenance of genome integrity. RecQ helicases were originally discovered in E COLI and are highly conserved across both prokaryotic and eukaryotic organisms. Genetic mutations that result in loss of RecQ helicase activity gives rise to disorders that are associated with CANCER predisposition and premature aging.	RecQ Family of DNA Helicase,RecQ Helicase,ATP-Dependent DNA Helicase Q1,ATP-Dependent DNA Helicase Q4,ATP-Dependent DNA Helicase Q5,DNA Helicase Q1,DNA Helicase RecQL,DNA Helicase RecQL4,DNA Helicase, RecQ-like type 2,DNA-Dependent ATPase Q1,RECQL1 Helicase,RTS Helicase,RecQ Family of DNA Helicases,RecQ Protein,RecQ2 Helicase,RecQ3 Helicase,RecQ4 Helicase,RecQ5 Helicase,RecQ5L Helicase,RecQL Helicase,RecQL2 Helicase,RecQL3 Helicase,RecQL4 Helicase,ATP Dependent DNA Helicase Q1,ATP Dependent DNA Helicase Q4,ATP Dependent DNA Helicase Q5,DNA Dependent ATPase Q1,DNA Helicase, RecQ like type 2,Helicase, RECQL1,Helicase, RTS,Helicase, RecQ,Helicase, RecQ2,Helicase, RecQ3,Helicase, RecQ5,Helicase, RecQ5L,Helicase, RecQL,Helicase, RecQL2,Helicase, RecQL3,Helicase, RecQL4,Helicases, RecQ