Chromatin

Publication Title: 
Aging

The FoxO family of transcription factors plays an important role in longevity and tumor suppression by regulating the expression of a wide range of target genes. FoxO3 has recently been found to be associated with extreme longevity in humans and to regulate the homeostasis of adult stem cell pools in mammals, which may contribute to longevity. The activity of FoxO3 is controlled by a variety of post-translational modifications that have been proposed to form a 'code' affecting FoxO3 subcellular localization, DNA binding ability, protein-protein interactions and protein stability.

Author(s): 
Calnan, Daniel R.
Webb, Ashley E.
White, Jamie L.
Stowe, Timothy R.
Goswami, Tapasree
Shi, Xiaobing
Espejo, Alexsandra
Bedford, Mark T.
Gozani, Or
Gygi, Steven P.
Brunet, Anne
Publication Title: 
Molecular Cell

Cellular processes function through multistep pathways that are reliant on the controlled association and disassociation of sequential protein complexes. While dynamic action is critical to propagate and terminate work, the mechanisms used to disassemble biological structures are not fully understood. Here we show that the p23 molecular chaperone initiates disassembly of protein-DNA complexes and that the GCN5 acetyltransferase prolongs the dissociated state through lysine acetylation.

Author(s): 
Zelin, Elena
Zhang, Yang
Toogun, Oyetunji A.
Zhong, Sheng
Freeman, Brian C.
Publication Title: 
Nucleic Acids Research

The eukaryotic DNA replication initiation factor Mcm10 is essential for both replisome assembly and function. Human Mcm10 has two DNA-binding domains, the conserved internal domain (ID) and the C-terminal domain (CTD), which is specific to metazoans. SIRT1 is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase that belongs to the sirtuin family. It is conserved from yeast to human and participates in cellular controls of metabolism, longevity, gene expression and genomic stability.

Author(s): 
Fatoba, Samuel T.
Tognetti, Silvia
Berto, Melissa
Leo, Elisabetta
Mulvey, Claire M.
Godovac-Zimmermann, Jasminka
Pommier, Yves
Okorokov, Andrei L.
Publication Title: 
Cellular and molecular life sciences: CMLS

Metabolic homeostasis and interventions that influence nutrient uptake are well-established means to influence lifespan even in higher eukaryotes. Until recently, the molecular mechanisms explaining such an effect remained scantily understood. Sirtuins are a group of protein deacetylases that depend on the metabolic intermediate NAD(+) as a cofactor for their function. For this reason they sense metabolic stress and in turn function at multiple levels to exert proper metabolic adaptation.

Author(s): 
Cosentino, Claudia
Mostoslavsky, Raul
Publication Title: 
Trends in Biochemical Sciences

In recent years there has been a large expansion in our understanding of SIRT6 biology including its structure, regulation, biochemical activity, and biological roles. SIRT6 functions as an ADP-ribosylase and NAD(+)-dependent deacylase of both acetyl groups and long-chain fatty-acyl groups. Through these functions SIRT6 impacts upon cellular homeostasis by regulating DNA repair, telomere maintenance, and glucose and lipid metabolism, thus affecting diseases such diabetes, obesity, heart disease, and cancer. Such roles may contribute to the overall longevity and health of the organism.

Author(s): 
Kugel, Sita
Mostoslavsky, Raul
Publication Title: 
Cell Cycle (Georgetown, Tex.)

Longevity, lifespan, cancer, cellular transformation, energy, calorie restriction, diabetes--what can tie together such a diversity of hot topics in biomedical research? Emerging findings suggest that the answer lies in understanding the functions of the recently discovered family of proteins known as Sirtuins. Barcelona hosted the first scientific meeting completely focused on these evolutionary conserved protein deacetylases, bringing together experts in the biochemistry to cellular biology, mice models, drug targeting and pathophysiology of these molecules.

Author(s): 
Mostoslavsky, Raul
Esteller, Manel
Vaquero, Alejandro
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Macronuclear telomeres in Oxytricha exist as DNA-protein complexes in which the termini of the G-rich strands are bound by a 97-kDa telomere protein. During telomeric DNA replication, the replication machinery must have access to the G-rich strand. However, given the stability of telomere protein binding, it has been unclear how this is accomplished. In this study we investigated the ability of several different DNA polymerases to access telomeric DNA in Oxytricha telomere protein-DNA complexes.

Author(s): 
Shippen, D. E.
Blackburn, E. H.
Price, C. M.
Publication Title: 
The Journal of Biological Chemistry

The chromatin structure of the 3'-nontranscribed spacer of the linear rRNA gene molecules of Tetrahymena thermophila was examined. This region includes the transcription termination site, two sets of recently identified conserved spacer repeats (Type IV and V repeats (Challoner, P. B., Amin, A. A., Pearlman, R. E., and Blackburn, E. H. (1985) Nucleic Acids Res. 13, 2661-2680], and the terminus of the molecule. Using sensitivity to nucleases as a probe, a unique chromatin structure was found in this rDNA region.

Author(s): 
Budarf, M. L.
Blackburn, E. H.
Publication Title: 
The Journal of Biological Chemistry

The chromatin structure of the 3'-nontranscribed spacer of the linear rRNA gene molecules of Tetrahymena thermophila was examined. This region includes the transcription termination site, two sets of recently identified conserved spacer repeats (Type IV and V repeats (Challoner, P. B., Amin, A. A., Pearlman, R. E., and Blackburn, E. H. (1985) Nucleic Acids Res. 13, 2661-2680], and the terminus of the molecule. Using sensitivity to nucleases as a probe, a unique chromatin structure was found in this rDNA region.

Author(s): 
Budarf, M. L.
Blackburn, E. H.
Publication Title: 
Journal of Molecular Biology

The telomeric d(GGGGTT).d(AACCCC) repeat tracts (G4T2 repeats) in Tetrahymena thermophila macronuclei were shown previously to be packaged in a non-nucleosomal DNA-protein complex. Here, we demonstrate that these telomeric repeats, together with a short region of the immediately adjacent non-telomeric sequence, exist in two distinct types of chromatin.

Author(s): 
Cohen, P.
Blackburn, E. H.

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