Our laboratory uses the budding yeast Saccharomyces cerevisiae as a model system to investigate fundamental questions in biology. One of our current areas of interest is understanding the striking link between increasing age and the incidence of cancer in humans. A hallmark of cancer, genomic instability, is observed in all types of organisms including yeast. We recently discovered that as yeast cells enter the middle-to-late period of their replicative lifespan, they switch to a state of high genomic instability that persists until death.We believe this change represents a fundamental transition in many aging cells and thus are taking a number of approaches to understand the mechanism underlying this phenomenon.

Selected Publications:

Lindstrom, DL, Gottschling, D.E.
The Mother Enrichment Program: A Genetic System for Facile Replicative Life Span Analysis in Saccharomyces cerevisiae.
Genetics. 2009 Oct;183(2):413-22, 1SI-13SI.

Dimitrov, L. N., R. B. Brem, L. Kruglyak and D. E. Gottschling.
Polymorphisms in multiple genes contribute to the spontaneous mitochondrial genome instability of S. cerevisiae S288C strains.
Genetics. 2009 Sep;183(1):365-83.

Veatch, J., McMurray, M.A., Nelson, Z., and D.E. Gottschling.
Mitochondrial Dysfunction Leads to Nuclear Genome Instability via an Iron-Sulfur Cluster Defect.
Cell. 2009 Jun 26;137(7):1247-58.

Van Welsem, T., Frederiks, F., Verzijlbergen, K. F., Faber, A. W., Nelson, Z. W., Egan, D. A.,Gottschling, D. E., van Leeuwen, F.
Synthetic lethal screens identify gene silencing processes in yeast and implicate the acetylated amino terminus of Sir3 in recognition of the nucleosome core.
Mol Cell Biol. 2008 Jun;28(11):3861-72.

Andersen, M. P.; Nelson, Z. W.; Hetrick, E. D.; Gottschling, D. E.
A genetic screen for increased loss of heterozygosity in Saccharomyces cerevisiae.
Genetics. 2008 Jul;179(3):1179-95.

D. E. Gottschling
DNA repair: corrections in the golden years.
Curr Biol. 2006 Nov 21;16(22):R956-8

R. G. Gardner, Z. W. Nelson & D. E. Gottschling
Ubp10/Dot4p Regulates the Persistence of Ubiquitinated Histone H2B: Distinct Roles in Telomeric Silencing and General Chromatin.
Mol Cell Biol. 2005 Jul;25(14):6123-39

R. G. Gardner, Z. W. Nelson & D. E. Gottschling
Degradation-mediated protein quality control in the nucleus.
Cell. 120(6):803-15 (2005)

E. Y. Xu, X. Bi, M. J. Holland, D. E. Gottschling & J. R. Broach
Mutations in the Nucleosome Core Enhance Transcriptional Silencing.
Mol Cell Biol. 25(5):1846-59 (2005)

D. E. Gottschling
Summary: epigenetics--from phenomenon to field.
Cold Spring Harb Symp Quant Biol. 2004;69:507-19

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