Meng-Chao Yao

powered by
COS Expertise®
Fred Hutchinson Cancer Research Center
Basic Sciences
Member
University of Washington
College of Arts and Sciences
Zoology
Affiliate ProfessorAppointed: 1988
Professional Headshot of Meng-Chao Yao

Mailing Address

1100 Fairview Ave. N.
P.O. Box 19024
Fred Hutchinson Cancer Research Center
Mailstop A2-168
Seattle, Washington 98109-1024
United States

Contact Information

Phone: (206) 667-5005
Fax: (206) 667-6526
mcyao@fhcrc.org

Qualifications

Ph.D., University of Rochester, Biology, 1975.

Expertise and Research Interests

Gene amplification, DNA rearrangements and chromosome instability in eukaryotes.

My laboratory uses the ciliate Tetrahymena and other eukaryotes including yeast and mammalian cells to study the mechanisms of DNA rearrangements, gene amplification and other processes that affect the integrity and transmission of eukaryotic genomes. Tetrahymena is particularly suited for these studies because it carries out a remarkable series of DNA rearrangements during somatic nuclear differentiation, including massive chromosome breakage, telomere formation and DNA deletion, as well as specific gene amplification. Recently we have identified several critical cis-acting sequences involved in these processes, including a 15 bp sequence necessary and sufficient for chromosome breakage, two sets of sequences that promote DNA deletion and specify deletion boundaries, and a pair of inverted repeats essential for large DNA palindrome formation during gene amplification. This information set the stage for further investigation of the underlying molecular mechanisms. We have also begun to identify proteins involved in these processes and found a novel protein pdd1p that shows close cytological and physically association with the deleted DNA during the process. This protein contains two chromodomains and is thought to play a key role in re-organizing chromatin during DNA rearrangements. Reverse genetics studies have shown that the protein is needed for successful nuclear differentiation and DNA deletion. In order to identify additional proteins, we have recently established a method to screen for proteins that are localized in developing nuclei, and have identified ten additional novel genes. We are determining their roles in DNA rearrangements and/or nuclear differentiation. Most recently, we have shown that the deletion process can remove inserted foreign sequences, and probably serves to defend the genome against invading genetic agents. Furthermore, injection of double stranded RNA triggers DNA deletion, demonstrating a mechanistic link between DNA deletion and RNA intereference that occur widely among eukaryotes.

At least one mechanism of DNA rearrangements discovered in Tetrahymena has also been found to occur in other organisms. We have shown that giant DNA palindromes can be produced in budding yeast by introducing a double stranded DNA break next to a pair of short inverted repeats, just like in Tetrahymena. This finding suggests a common mechanism for generating amplified genetic elements in eukaryotes. We have now successfully tested this idea using Chinese hamster ovary cells, and begun to examine the role of this mechanism in gene amplification and cancer progression.

Other Expertise

The biogenesis and function of ribosomal RNA.

Keywords

COS Keywords:

Biochemistry, Biophysics, Cell Biology, Developmental Biology, Developmental Genetics, DNA Replication, Genetics, Human Physiology, Pharmacology.

Additional Terms:

CHO Cells, Cell Transformation, Chromosome Aberration, Ciliates, DNA Binding Protein, DNA Replication, Developmental Genetics, Gel Mobility Shift Assay, Gene Amplification, Gene Deletion Mutation, Gene Rearrangement, Genetic Regulatory Element, Genome, Microorganism Genetics, Mutant, Nucleic Acid Sequence, Ribosomal DNA, Ribosomal RNA, Telomere, Tetrahymena, Transcription Factor, Western Blotting.

Languages

(Reading, Writing, Speaking)

Chinese, Mandarin: (Fluent, Functional, Fluent)

Memberships

American Association for the Advancement of Science
American Society for Cell Biology
Society of Protozoologists

Honors and Awards

Fellow, American Association for the Advancement of Science (AAAS)

Previous Positions

1978-1986, Assistant and Associate Professor, Washington University in St. Louis, Arts and Sciences, Biology

Patents

Ribosomes as vectors for RNA, Patent Number: 5739310, 1998, Institution-owned, United States of America.

Funding Received

  • National Cancer Institute: Pilot Project: A new approach to gene amplification in tumor cells., Jan 1, 2001 to Dec 31, 2002.
  • National Cancer Institute: Training Grant: Chromosome metabolism and cancer, 1991 to 2006.
  • NIH R01 GM26210: Chromosome Breakage and DNA Deletion in Tetrahymena, 1979 to 2006.

Publications

  • Wiley EA, Myers T, Parker K, Braun T, Yao MC (May 2005) Class I histone deacetylase Thd1p affects nuclear integrity in Tetrahymena thermophila, Eukaryotic Cell, 4 (5), 981-90
  • Tanaka H, Bergstrom DA, Yao MC, Tapscott SJ (Mar 2005) Widespread and nonrandom distribution of DNA palindromes in cancer cells provides a structural platform for subsequent gene amplification, Nature Genetics, 37 (3), 320-7
  • Yao, M.-C., Chao J. (2005) RNA-guided DNA deletion in Tetrahymena: an RNAi-based mechanism for programmed genome rearrangements, Annual Review of Genetics, 39, 537-559
  • Chalker DL, Fuller P, Yao MC (Jan 2005) Communication between parental and developing genomes during tetrahymena nuclear differentiation is likely mediated by homologous RNAs, Genetics, 169 (1), 149-60
  • Yao MC, Fuller P, Xi X, Programmed DNA deletion as an RNA-guided system of genome defense, Science, 300(5625), 1581-4, June 2003 Abstract
  • Tanaka H, Tapscott SJ, Trask BJ, Yao MC, Short inverted repeats initiate gene amplification through the formation of a large DNA palindrome in mammalian cells, Proceedings of the National Academy of Sciences (USA), 99(13), 8772-7, June 2002 Abstract
  • Duharcourt S, Yao MC, Role of histone deacetylation in developmentally programmed DNA rearrangements in Tetrahymena thermophila, Eukaryotic Cell, 1(2), 293-303, April 2002 Abstract
  • Yao, M.-C., Duharcourt, S. and Chalker, D., 'Genome-wide rearrangements of DNA in ciliates', in Mobile DNA II. N. Craig, R. Craigie, M. Gellert and A. Lambowitz, editors; ASM Press, Washington, D.C., 730-758, 2002
  • Chalker DL, Yao MC, Nongenic, bidirectional transcription precedes and may promote developmental DNA deletion in Tetrahymena thermophila, Genes and Development, 15(10), 1287-98, 2001 Abstract
  • Wiley EA, Ohba R, Yao MC, Allis CD, Developmentally regulated rpd3p homolog specific to the transcriptionally active macronucleus of vegetative Tetrahymena thermophila, Molecular and Cellular Biology, 20(22), 8319-28, November 2000 Abstract
  • Fan Q, Yao MC, A long stringent sequence signal for programmed chromosome breakage in Tetrahymena thermophila, Nucleic Acids Research, 28(4), 895-900, February 2000 Abstract
  • Coyne RS, Nikiforov MA, Smothers JF, Allis CD, Yao MC, Parental expression of the chromodomain protein Pdd1p is required for completion of programmed DNA elimination and nuclear differentiation, Molecular Cell, 4(5), 865-72, November 1999 Abstract
  • Chalker DL, La Terza A, Wilson A, Kroenke CD, Yao MC, Flanking regulatory sequences of the Tetrahymena R deletion element determine the boundaries of DNA rearrangement., Molecular and Cellular Biology, 19(8), 5631-41, August 1999 Abstract
  • Erbeznik, M., Yao, M.-C. and Jahn, C. L., Characterization of the Euplptes crassus macronuclear rDNA and its potential as a DNA transformation vehicle, Journal of Eukaryotic Microbiology, 46, 206-216., 1999
  • Sweeney R, Yao M C, An intragenic suppressor of cold sensitivity identifies potentially interacting bases in the peptidyl transferase center of Tetrahymena rRNA., Genetics, 149(2), 937-46, June 1998 Abstract
  • Sweeney R, Fan Q, Yao M C, Antisense in abundance: the ribosome as a vehicle for antisense RNA., Genetic Engineering, 20, 143-51, 1998 Abstract
  • Blomberg P, Randolph C, Yao C H, Yao M C, Regulatory sequences for the amplification and replication of the ribosomal DNA minichromosome in Tetrahymena thermophila., Molecular and Cellular Biology, 17(12), 7237-47, December 1997 Abstract
  • Ward J G, Blomberg P, Hoffman N, Yao M C, The intranuclear organization of normal, hemizygous and excision-deficient rRNA genes during developmental amplification in Tetrahymena thermophila., Chromosoma, 106(4), 233-42, September 1997 Abstract
  • Butler D K, Yasuda L E, Yao M C, Induction of large DNA palindrome formation in yeast: implications for gene amplification and genome stability in eukaryotes., Cell, 87(6), 1115-22, 13 Dec 1996 Abstract
  • Coyne R S, Yao M C, Evolutionary conservation of sequences directing chromosome breakage and rDNA palindrome formation in tetrahymenine ciliates., Genetics, 144(4), 1479-87, December 1996 Abstract
  • Madireddi M T, Coyne R S, Smothers J F, Mickey K M, Yao M C, Allis C D, Pdd1p, a novel chromodomain-containing protein, links heterochromatin assembly and DNA elimination in Tetrahymena., Cell, 87(1), 75-84, 4 Oct 1996 Abstract
  • Sweeney R, Fan Q, Yao M C, Antisense ribosomes: rRNA as a vehicle for antisense RNAs., Proceedings of the National Academy of Sciences (USA), 93(16), 8518-23, 6 Aug 1996 Abstract
  • Chalker D L, Yao M C, Non-Mendelian, heritable blocks to DNA rearrangement are induced by loading the somatic nucleus of Tetrahymena thermophila with germ line-limited DNA., Molecular and Cellular Biology, 16(7), 3658-67, July 1996 Abstract
  • Fan Q, Yao M, New telomere formation coupled with site-specific chromosome breakage in Tetrahymena thermophila., Molecular and Cellular Biology, 16(3), 1267-74, March 1996 Abstract
  • Coyne R S, Chalker D L, Yao M C, Genome downsizing during ciliate development: nuclear division of labor through chromosome restructuring., Annual Review of Genetics, 30, 557-78, 1996 Abstract
  • Yao M C, Programmed DNA deletions in Tetrahymena: mechanisms and implications., Trends In Genetics, 12(1), 26-30, January 1996 Abstract
  • Butler D K, Yasuda L E, Yao M C, An intramolecular recombination mechanism for the formation of the rRNA gene palindrome of Tetrahymena thermophila., Molecular and Cellular Biology, 15(12), 7117-26, December 1995 Abstract
  • Yao M C, Yao C H, Detection of circular excised DNA deletion elements in Tetrahymena thermophila during development., Nucleic Acids Research, 22(25), 5702-8, 25 Dec 1994 Abstract
  • Sweeney R, Chen L, Yao M C, An rRNA variable region has an evolutionarily conserved essential role despite sequence divergence., Molecular and Cellular Biology, 14(6), 4203-15, June 1994 Abstract
  • Godiska R, James C, Yao M C, A distant 10-bp sequence specifies the boundaries of a programmed DNA deletion in Tetrahymena., Genes and Development, 7(12A), 2357-65, December 1993 Abstract
  • Sweeney R, Chen L, Yao M C, Phenotypic effects of targeted mutations in the small subunit rRNA gene of Tetrahymena thermophila., Molecular and Cellular Biology, 13(8), 4814-25, August 1993 Abstract
  • Yasuda L F, Yao M C, Short inverted repeats at a free end signal large palindromic DNA formation in Tetrahymena., Cell, 67(3), 505-16, 1 Nov 1991 Abstract
  • Yao M C, Yao C H, Transformation of Tetrahymena to cycloheximide resistance with a ribosomal protein gene through sequence replacement., Proceedings of the National Academy of Sciences (USA), 88(21), 9493-7, 1 Nov 1991 Abstract
  • Sweeney R, Yao C H, Yao M C, A mutation in the large subunit ribosomal RNA gene of Tetrahymena confers anisomycin resistance and cold sensitivity., Genetics, 127(2), 327-34, February 1991 Abstract
  • Yao M C, Yao C H, Monks B, The controlling sequence for site-specific chromosome breakage in Tetrahymena., Cell, 63(4), 763-72, 16 Nov 1990 Abstract
  • Godiska R, Yao M C, A programmed site-specific DNA rearrangement in Tetrahymena thermophila requires flanking polypurine tracts., Cell, 61(7), 1237-46, 29 Jun 1990 Abstract
  • Sweeney R, Yao M C, Identifying functional regions of rRNA by insertion mutagenesis and complete gene replacement in Tetrahymena thermophila., Embo Journal, 8(3), 933-8, March 1989 Abstract

Profile Details

Last Updated: 4/16/2006

COS Expertise ID #546673
Reference this profile directly: http://myprofile.cos.com/mcyao