Jeffrey N. Strathern, Ph.D.
Jeffrey N. Strathern, Ph.D.
Chief
Senior Investigator
Head, Genome Recombination and Regulation Section
CCR Deputy Director

Center for Cancer Research
National Cancer Institute

Building 539, Room 152E
Frederick, MD 21702-1201
301-846-1274

Two general areas of research are pursued in our section: mechanisms of genetic recombination and mechanisms of gene regulation. We are focused on the area of genetic recombination in general and double-strand-break repair in particular. DNA palindromes are thought to be a common mechanism of gene amplification found in tumor cells. However, palindromes are particularly difficult to investigate because they are difficult to clone and difficult to sequence. We created yeast strains that tolerate DNA palindromes and developed system in which they can be generated.

Areas of Expertise
genetic recombination, gene regulation

Two general areas of research are pursued in our section: mechanisms of genetic recombination and mechanisms of gene regulation. We are focused on the area of genetic recombination in general and double-strand-break repair in particular. We demonstrated that the DNA synthesis associated with genetic recombination has substantially lower fidelity than that found in general cell duplication. At least two different DNA polymerases have roles in this elevated mutation rate: Base substitutions reverting a non-sense allele are dependent on the translesion polymerase, Pol zeta, encoded by REV3, whereas reversion of frameshift alleles is REV3 independent. We continue to investigate the mechanism of double-strand-break repair and the proteins involved in controlling the fidelity of DNA synthesis during this process. We extended this research to demonstrate meiotic recombination is also mutagenic. DNA palindromes are thought to be a common mechanism of gene amplification found in tumor cells. However, palindromes are particularly difficult to investigate because they are difficult to clone and difficult to sequence. We created yeast strains that tolerate DNA palindromes and developed system in which they can be generated. We also developed a method to sequence DNA palindromes. We are applying these tools to the characterization of DNA palindromes isolated from human tumor cell lines.

We also study the fidelity of transcription. Again, a historically difficult problem for which we developed a genetic screen to identify mutants with reduced fidelity. 

We have isolated mutations that reduce the fidelity of transcription and have identified mutations in several subunits of RNA polymerase that result in error prone transcription. 

We are now studying the consequences of increased transcription error rates.

Our collaborators are Stephen Hughes, Michael Kashlev and Ding Jin, NCI.

Scientific Focus Areas:
Chromosome Biology, Genetics and Genomics, Molecular Biology and Biochemistry
Selected Publications
  1. Imashimizu M, Kireeva ML, Lubkowska L, Gotte D, Parks AR, Strathern JN, Kashlev M.
    J. Mol. Biol. 425: 697-712, 2013. [ Journal Article ]
  2. Zhou YN, Lubkowska L, Hui M, Court C, Chen S, Court DL, Strathern J, Jin DJ, Kashlev M.
    J. Biol. Chem. 288: 2700-10, 2013. [ Journal Article ]
  3. Strathern J, Malagon F, Irvin J, Gotte D, Shafer B, Kireeva M, Lubkowska L, Jin DJ, Kashlev M.
    J. Biol. Chem. 288: 2689-99, 2013. [ Journal Article ]
  4. Strathern JN, Jin DJ, Court DL, Kashlev M.
    Biochim Biophys Acta B. 1819: 694-9, 2012. [ Journal Article ]
  5. Walmacq C, Cheung AC, Kireeva ML, Lubkowska L, Ye C, Gotte D, Strathern JN, Carell T, Cramer P, Kashlev M.
    Mol. Cell. 46: 18-29, 2012. [ Journal Article ]

Dr. Strathern obtained his Ph.D. from the Molecular Biology Institute at the University of Oregon in 1977, then moved to Cold Spring Harbor Laboratory where he became a senior staff member with the Yeast Genetics Laboratory. In 1984, he joined the ABL-Basic Research Program at the NCI's Frederick Cancer Research Development Center (now NCI-Frederick). His research remains centered on aspects of gene regulation and genetic recombination as revealed by studies in yeast. In 1999, Dr. Strathern joined the Division of Basic Sciences, NCI. In March 2001, the Division of Basic Sciences merged with the Division of Clinical Sciences to form the NCI Center for Cancer Research. In addition to his roles as Chief of GRCBL and Head of the Gene Regulation and Recombination Section, Dr. Strathern is a Deputy Director for the NCI-Center for Cancer Research.

Name Position
Charlotte Choi Postbaccalaureate Fellow
Mary K. Ernst Senior Research Assistant
Kevin Franco Special Volunteer
Deanna Gotte Research Assistant
Jordan D. Irvin Ph.D. Special Volunteer
Alison J. Rattray Ph.D. Staff Scientist
Brenda Shafer Research Assistant
Cyndi Trang Postbaccalaureate Fellow
Hui Yang Ph.D. Research Fellow

Summary

Two general areas of research are pursued in our section: mechanisms of genetic recombination and mechanisms of gene regulation. We are focused on the area of genetic recombination in general and double-strand-break repair in particular. DNA palindromes are thought to be a common mechanism of gene amplification found in tumor cells. However, palindromes are particularly difficult to investigate because they are difficult to clone and difficult to sequence. We created yeast strains that tolerate DNA palindromes and developed system in which they can be generated.

Areas of Expertise
genetic recombination, gene regulation

Research

Two general areas of research are pursued in our section: mechanisms of genetic recombination and mechanisms of gene regulation. We are focused on the area of genetic recombination in general and double-strand-break repair in particular. We demonstrated that the DNA synthesis associated with genetic recombination has substantially lower fidelity than that found in general cell duplication. At least two different DNA polymerases have roles in this elevated mutation rate: Base substitutions reverting a non-sense allele are dependent on the translesion polymerase, Pol zeta, encoded by REV3, whereas reversion of frameshift alleles is REV3 independent. We continue to investigate the mechanism of double-strand-break repair and the proteins involved in controlling the fidelity of DNA synthesis during this process. We extended this research to demonstrate meiotic recombination is also mutagenic. DNA palindromes are thought to be a common mechanism of gene amplification found in tumor cells. However, palindromes are particularly difficult to investigate because they are difficult to clone and difficult to sequence. We created yeast strains that tolerate DNA palindromes and developed system in which they can be generated. We also developed a method to sequence DNA palindromes. We are applying these tools to the characterization of DNA palindromes isolated from human tumor cell lines.

We also study the fidelity of transcription. Again, a historically difficult problem for which we developed a genetic screen to identify mutants with reduced fidelity. 

We have isolated mutations that reduce the fidelity of transcription and have identified mutations in several subunits of RNA polymerase that result in error prone transcription. 

We are now studying the consequences of increased transcription error rates.

Our collaborators are Stephen Hughes, Michael Kashlev and Ding Jin, NCI.

Scientific Focus Areas:
Chromosome Biology, Genetics and Genomics, Molecular Biology and Biochemistry

Publications

Selected Publications
  1. Imashimizu M, Kireeva ML, Lubkowska L, Gotte D, Parks AR, Strathern JN, Kashlev M.
    J. Mol. Biol. 425: 697-712, 2013. [ Journal Article ]
  2. Zhou YN, Lubkowska L, Hui M, Court C, Chen S, Court DL, Strathern J, Jin DJ, Kashlev M.
    J. Biol. Chem. 288: 2700-10, 2013. [ Journal Article ]
  3. Strathern J, Malagon F, Irvin J, Gotte D, Shafer B, Kireeva M, Lubkowska L, Jin DJ, Kashlev M.
    J. Biol. Chem. 288: 2689-99, 2013. [ Journal Article ]
  4. Strathern JN, Jin DJ, Court DL, Kashlev M.
    Biochim Biophys Acta B. 1819: 694-9, 2012. [ Journal Article ]
  5. Walmacq C, Cheung AC, Kireeva ML, Lubkowska L, Ye C, Gotte D, Strathern JN, Carell T, Cramer P, Kashlev M.
    Mol. Cell. 46: 18-29, 2012. [ Journal Article ]

Biography

Dr. Strathern obtained his Ph.D. from the Molecular Biology Institute at the University of Oregon in 1977, then moved to Cold Spring Harbor Laboratory where he became a senior staff member with the Yeast Genetics Laboratory. In 1984, he joined the ABL-Basic Research Program at the NCI's Frederick Cancer Research Development Center (now NCI-Frederick). His research remains centered on aspects of gene regulation and genetic recombination as revealed by studies in yeast. In 1999, Dr. Strathern joined the Division of Basic Sciences, NCI. In March 2001, the Division of Basic Sciences merged with the Division of Clinical Sciences to form the NCI Center for Cancer Research. In addition to his roles as Chief of GRCBL and Head of the Gene Regulation and Recombination Section, Dr. Strathern is a Deputy Director for the NCI-Center for Cancer Research.

Team

Name Position
Charlotte Choi Postbaccalaureate Fellow
Mary K. Ernst Senior Research Assistant
Kevin Franco Special Volunteer
Deanna Gotte Research Assistant
Jordan D. Irvin Ph.D. Special Volunteer
Alison J. Rattray Ph.D. Staff Scientist
Brenda Shafer Research Assistant
Cyndi Trang Postbaccalaureate Fellow
Hui Yang Ph.D. Research Fellow