Most of my research has focused on retrotransposons, which are a type of mobile DNA element. Many copies of retrotransposon sequences are present in a variety of different organisms, and in some cases they comprise a large fraction of the genomic DNA in an organism. For instance, almost half of the human genome consists of different types of retrotransposon sequences. Retrotransposon DNA sequences are transcribed into RNA copies that are used as templates by retrotransposon-encoded reverse transcriptase proteins to produce a new DNA copy of the retrotransposon RNA that is integrated into a genomic site. This is referred to as a copy-and-paste retrotransposition mechanism that results in an extra copy of the original retrotransposon at a different genomic region. Retrotransposons can directly or indirectly contribute to the occurrence of DNA damage, new mutations, chromosome rearrangements, and changes in patterns of gene expression that can influence cell growth and survival. My work on retrotransposons began (Syracuse University) with studies of telomeric retrotransposons in the fruit fly, Drosophila melanogaster. Fruit fly telomeres (chromosome ends) are exceptional because they are maintained by retrotransposition of specific retrotransposons to chromosome ends, and this provides a clear case of retrotransposons providing a benefit to an organism. I then moved on (Wadsworth Center, Albany, NY) to study the consequences of activation of retrotransposons in cells lacking functional telomerase enzyme in baker’s yeast, Saccharomyces cerevisiae. Telomerase is the enzyme that maintains DNA at the ends of linear chromosomes (telomeres) in many organisms, but yeast cells can adapt to the absence of telomerase and continue to proliferate. I found that activation of retrotransposons in yeast telomerase mutants resulted in these elements producing reverse transcripts of other cellular RNA and incorporation of those DNA copies into the yeast genome. Incorporation of those retrosequences (reverse transcripts) into the genome frequently resulted in chromosome rearrangements. These earlier studies ultimately led me to pursue the possible contribution of retrotransposons to genetic damage that accumulates with age. Aging is an obvious characteristic of organisms, but it is still incompletely understood at the cell and molecular level. Genes involved in growth control or stress responses, basic cellular processes such as mitochondrial function and protein degradation, changes in chromatin that alter overall gene expression, and accumulation of DNA damage or mutations are some examples of factors that are considered to contribute to the rate of aging. Retrotransposons have recently emerged as factors that might influence aging in multiple organisms through their ability to damage/alter genomes and to influence gene expression. My research group is continuing to make use of baker’s yeast to study how retrotransposons are involved in the aging process. Yeast lifespan is measured as the length of time cells remain viable in a non-dividing state (chronological lifespan) or as the number of daughter cells that a mother cell can produce (replicative lifespan). Remarkably, a number of factors influencing yeast aging are similar to those that influence aging of other multicellular organisms (such as processes and factors noted above). Baker’s yeast also offers some advantages for addressing this topic, including the availability of yeast strains with no retrotransposons in their genomes and experimental methods to easily quantify the rate of retrotransposition. My group’s work involves both chronological aging and replicative aging of yeast cells, and for the latter we make use of a magnetic cell-sorting protocol for isolating mother cells from their daughter cells. We are testing 1) the regulation of retrotransposons during aging, 2) whether the presence or activity of these elements alters lifespan in different contexts, and 3) specifically how their retrotransposition or expression may contribute to genetic damage or changes in gene expression. We are pursuing both potential positive and negative influences of these elements on aging by examining how their presence and expression may alter cell growth, mitochondrial function, and stress responses. Work involves cell biology, molecular biology, and genetic approaches, such as: engineering yeast cells to have specific mutations or reporter genes, analyzing mutations and chromosome-scale genome rearrangements, measuring mitochondrial function and reactive oxygen species, examining sensitivity/responses to stresses, and examining gene expression/activity in relevant genetic pathways. We are also more broadly examining how DNA damage and accumulation of genetic changes relate to the aging process.
B.S. State University of New York College at Cortland (Biology), Ph.D. Syracuse University (Molecular Biology)
- Maxwell, P. H. (2016). What might retrotransposons teach us about aging? Curr. Genet. 62(2):277-282. PMID: 26581630
- Patterson, M. N., Scannapieco, A. E., Au, P. H., Dorsey, S., Royer, C. A., and Maxwell, P. H. (2015). Preferential retrotransposition in aging yeast mother cells is correlated with increased genome instability. DNA Repair 34:18-27. PMID: 26298836
- Maxwell, P. H. (2014). Consequences of ongoing retrotransposition in mammalian genomes. Advances in Genomics and Genetics 4:129-142.
- VanHoute, D. and Maxwell, P. H. (2014). Extension of Saccharomyces paradoxus chronological lifespan by retrotransposons in certain media conditions is associated with changes in reactive oxygen species. Genetics 198(2):531-545. PMID: 25106655
- Patterson, M. N. and Maxwell, P. H. (2014). Combining magnetic sorting of mother cells and fluctuation tests to analyze genome instability during mitotic cell aging in Saccharomyces cerevisiae. J Vis Exp Oct 16;(92). PMID 25350605
- Maxwell, P. H., Burhans, W. C., and Curcio, M. J. (2011). Retrotransposition is associated with genome instability during chronological aging. Proc. Natl. Acad. Sci. USA 108(51):20376-20381. PMCID: PMC3251071
- Stamenova, R., Maxwell, P. H., Kenny A. E., and Curcio, M. J. (2009). Rrm3 protects the genome from instability at nascent sites of retrotransposition. Genetics 182(3):711-723. PMCID: PMC2710153
- Maxwell, P. H. and Curcio, M. J. (2008). Incorporation of Y’-Ty1 cDNA destabilizes telomeres in Saccharomyces cerevisiae telomerase-negative mutants. Genetics 179(4): 2313-2317. PMCID: PMC2516100
- Maxwell, P. H., Belote, J. M., and Levis, R. W. (2008). Developmental and tissue-specific accumulation pattern for the Drosophila melanogaster TART ORF1 protein. Gene 415(1-2): 32-39.