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Kenan Distinguished Professor
11-127 LCCC

Structure of telomeres: how they control cell aging and death


Telomeres contain ~1/3000th the DNA in a human cell, yet shelter us from oncogenic progression, monitor the number of cell divisions and respond to toxic insult from agents producing DNA damage. This is accomplished via pathways which signal the presence of DNA lesions. A central feature of the telomere is its 3-dimensional structure.  In 1999 we showed that the ends of mammalian telomeres loop back and invade the preceding telomeric DNA. T-loops have now been found from humans to yeast (with genetic manipulation). Recently Doksani in the de Lange and Zhang labs used STORM light microscope imaging to confirm the presence of t-loops in mouse cells and observed loop frequencies and dimensions similar to what we observed by EM.   Telomeres are rich in complex structural elements including the t-loop, t-loop junction (more complex than previously believed), and R-loops. The latter are a recently recognized component of telomeres. R-loops can lead to genomic instability, gross chromosomal rearrangements, and cancer. R-loops may represent one of the greatest threats to telomeres yet may be needed to form protective t-loops. Our current work is focused on understanding more about the role of R-loops at the telomere using a variety of structural and biochemical tools including electron microscopy.

Selected publications

Nadalutti CA, Stefanick DF, Zhao ML, Horton JK, Prasad R, Brooks AM, Griffith JD, and Wilson SH. (2020). Mitochondrial dysfunction and DNA damage accompany enhanced levels of formaldehyde in cultured primary human fibroblasts. Sci Rep. 2020 Mar 27;10(1):5575. doi: 10.1038/s41598-020-61477-2 PMID:32221313

Tsutakawa, S. E., Sarker, A. H., Ng, C., Arvai, A. S., Shin, D. S., Shih, B., Jiang, S., Thwin, A. C., Tsai, M. S., Willcox, A., Her, M. Z., Trego, K. S., Raetz, A. G., Rosenberg, D., Bacolla, A., Hammel, M., Griffith, J. D., Cooper, P. K., & Tainer, J. A. (2020). Human XPG nuclease structure, assembly, and activities with insights for neurodegeneration and cancer from pathogenic mutations. Proc Natl Acad Sci U S A, 117(25), 14127-14138. doi:10.1073/pnas.1921311117. PMC7321962. 04-VIR

Griffith JD. Electron microscopic characterization of exhaust particles containing lead dibromide beads expelled from aircraft burning leaded gasoline. Atmos Pollut Res. 2020 Sep;11(9):1481-1486. doi: 10.1016/j.apr.2020.05.026. Epub 2020 Jun 4. PMID: 33100835; PMCID: PMC7583388.

Tomáška Ľ, Cesare AJ, Al-Turki TM, and Griffith JD. (2020) Twenty years of t-loops: A case study for the importance of collaboration in molecular biology.  DNA Repair (Amst). Jun 26:102901. doi: 10.1016/j.dnarep.2020.102901.  PMID: 32620538

Photographic Society of America.  Progress Award

The photographic society of America  (PSA) has over 6000 members in 80 different countries making it the largest society dedicated to photography.  Each year the PSA presents its Progress Award for the advancement of photography.  Previous awardees include Walt Disney (1952); Henry Luce, Life Magazine (1954); Edward Weston (1957); Edwin Land, Polaroid (1960), Melville Grosvenor, Natl. Geographic (1963), Capt. Edward Steichen,  Family of Man, (1967);  Ansel Adams, (1969); Dr. Victor Hasselblad, (1971); Jacques-Yves Cousteau (1977);  Lennart Nilsson, medical video, (1997); and Thomas and John Knoll (Adobe Photoshop, (2001).   This year (2020/21 ) Jack was honored for using photo-microscopy with the electron microscope to reveal details of DNA mechanics and organization.

List of My Bibliography