Daniel Gottschling
Member, Fred Hutchinson Cancer Research Center
Affiliate Professor of Genome Sciences

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.

Publications:

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

M. A. McMurray & D. E. Gottschling
Genetic instability in aging yeast: a metastable hyperrecombinational state.
Cold Spring Harb Symp Quant Biol. 2004;69:339-47

M. A. McMurray & D. E. Gottschling
Aging and genetic instability in yeast.
Curr Opin Microbiol 7(6):673-9 (2004)

A. E. Stellwagen, Z. H. Haimberger, J. R. Veatch & D. E. Gottschling Ku interacts with telomerase RNA to promote telomere addition at native and broken chromosome ends. Genes Dev 17(19):2384-2395 (2003)

M. A. McMurray & D. E. Gottschling An age-induced switch to a hyper-recombinational state. Science 301(5641):1908-11 (2003)

C. M. Smith, P. R. Hafken, Z. Zhang, D. E. Gottschling, J. B. Smith & D. L. Smith Mass spectrometric quantification of acetylation at specific lysines within the amino-terminal tail of histone H4. Anal Biochem 316(1):23-33 (2003)

F. van Leeuwen & D. E. Gottschling The histone minority report: the variant shall not be silenced. Cell 112(5):591-3 (2003)

F. van Leeuwen & D. E. Gottschling Genome-wide histone modifications: gaining specificity by preventing promiscuity. Curr Opin Cell Biol 14(6):756-62 (2002)

C. M. Smith, Z. W. Haimberger, C. O. Johnson, A. J. Wolf, P. R. Gafken, Z. Zhang, M. R. Parthun, & D. E. Gottschling Heritable chromatin structure: mapping "memory" in histones H3 and H4. Proc Natl Acad Sci U S A 99 Suppl 4:16454-61 (2002)

M. L. DuBois, Z. W. Haimberger, M. W. McIntosh, & D. E. Gottschling A Quantitative Assay for Telomere Protection in Saccharomyces cerevisiae. Genetics 161:995-1013 (2002)

F. van Leeuwen & D. E. Gottschling Assays for gene silencing in yeast. Methods Enzymol 350:165-86 (2002)

F. van Leeuwen, P. R. Gafken, & D. E. Gottschling Dot1p modulates silencing in yeast by methylation of the nucleosome core. Cell 109(6):745-56 (2002)

A. Bedalov, T. Gatbonton, W. P. Irvine, D. E. Gottschling, & J. A. Simon Identification of a small molecule inhibitor of Sir2p. Proc Natl Acad Sci U S A 98(26):15113-15118 (2001)

additional publication listings available via PubMed