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Prof. Mary-Lou Pardue
Professor of Biology, Emeritus
Primary DLC
Department of Biology
MIT Room:
68-670A
(617) 253-6741
mlpardue@mit.edu
Areas of Interest and Expertise
Cell Biochemistry
Structure and Function of Genetic Materials in Eukaryotes
Control of Gene Expression During Development
Heat Shock Response
Insect Viruses
Transposable Elements
RNA Metabolism
Telomeres
Genetics
Cell Biology
Biological Oceanography
Research Summary
Telomeres (the ends of chromosomes) have important roles in chromosome replication, in cell division, and in the cell-type-specific architecture of interphase nuclei. We know that telomere biology is fundamental to important aspects of cell biology, including cellular senescence, cell cycle checkpointing, organismal aging, and tumorigenesis, but we still know little about the mechanisms involved. Telomeres are complex and dynamic nucleoprotein structures formed on long arrays of repeated DNA sequences. In most organisms telomeres are maintained by an enzyme, telomerase. This enzyme compensates for erosion of chromosome ends by adding new repeats to the telomere array. These repeats are very short DNA sequences copied from the enzyme’s RNA template.
We study Drosophila telomeres, the original genetic and cytological model for telomeres. Drosophila telomeres are functionally similar to telomeres in other organisms but have an unexpected molecular difference: We have found that Drosophila telomeres are maintained, not by telomerase, but by special transposable elements, the retrotransposons, HeT-A, TART, and TAHRE. These elements transpose by reverse transcription directly onto the end of the chromosome (using their poly(A)+ RNA). Successive transpositions form long arrays of head-to-tail repeats. These repeats are analogous to the repeats added by telomerase except that the Drosophila repeats are copies of the retrotransposons, three orders of magnitude longer than the repeats added by telomerase. In spite of the length of individual repeats on Drosophila telomeres, the repeat arrays on Drosophila chromosome ends are similar in length to telomere arrays in other multicellular organisms. Because both the retrotransposons and telomerase extend telomeres by adding copies of an RNA template, the Drosophila and telomerase mechanisms are basically variants on the same theme. Not only are Drosophila telomeres structurally similar to telomerase telomeres, they interact functionally with homologues of many proteins that interact with telomerase telomeres.
The Drosophila telomeric retrotransposons are also unusual transposable elements. They are the first such elements shown to be entirely devoted to an essential cellular function. (Like their close relatives, the retroviruses, transposable elements are generally considered to be parasitic.) Drosophila telomeres provide a link between telomeres and transposable elements that raises interesting questions about the evolution of eukaryotic chromosomes. However, whatever their origin, these variant telomeres offer new insights into telomere structure and function.
Recent Work
Projects
December 5, 2011
Department of Biology
Sequences of Assembled Telomere Arrays Record the History of Events on the Ends of Chromosomes
Principal Investigator
Mary-Lou Pardue
December 5, 2011
Department of Biology
The Assembled Telomere Arrays Provide Sufficient Data for Quantitative Analysis of Events at the Ends of Telomere Arrays
Principal Investigator
Mary-Lou Pardue
December 5, 2011
Department of Biology
Telomere-Specific Retrotransposons Have Evolved Novel Ways to Protect Their 5’ Ends
Principal Investigator
Mary-Lou Pardue
December 5, 2011
Department of Biology
Differential Maintenance of Sequence in Telomeric and Centromeric Heterochromatin
Principal Investigator
Mary-Lou Pardue
December 19, 2006
Department of Biology
Novel Retroelement Promoters
Principal Investigator
Mary-Lou Pardue
March 30, 2004
Department of Biology
Potential Roles for Gag Proteins in Retroelement Targeting
Principal Investigator
Mary-Lou Pardue
March 3, 2004
Department of Biology
Phylogenetic Studies of Telomere-Specific Retrotransposons
Principal Investigator
Mary-Lou Pardue
Related Faculty
Dr. Christian Rueckert
Research Affiliate
Prof. Gerald R Fink
Margaret and Herman Sokol Professor of Biology
Prof. H Robert Horvitz
David H Koch Professor of Biology