Schulich school of Medicine and Dentistry logo Department of Biochemistry Schulich School of Medicine & Dentistry

Dr. Megan Jeanette Davey (1966 - 2012)

Associate Professor
B. Sc. York University
Ph.D. University of Toronto
Post-Doctoral Researcher, HHMI Rockefeller University

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DNA Replication: Nature’s Version of Photocopying

Our ability to copy information has advanced significantly since ancient times when monks painstakingly duplicated original texts manually. The discovery of electrophotography, the basis of photocopying, heralded the era of electronic copying. Today,we use multifunctional photocopiers that not only copy and collate, but also scan and send e-mails, almost before our fingers have left the machine’s start button. Nature, always a step ahead of us, has also developed an efficient system for copying information, namely, DNA replication to duplicate our genetic material.

DNA replication is an essential process by which cells copy their DNA sequences during cell division. Similar to multi-part photocopiers, nature’s copying machinery comprises multiple components: specific protein complexes perform sequentially the steps of initiation, elongation, and termination during the copying process. In eukaryotes, initiation of replication starts at multiple, specific DNA sites called origins. Here, the two complementary DNA strands are unwound by specialized enzymes called helicases to expose the nucleotide sequences for copying. Subsequent DNA synthesis on these template strands produces four-stranded structures known as replication forks. Termination of replication occurs when these forks meet during DNA elongation in the copying process.  

In eukaryotes, the replicative helicase is thought to be the MCM2-7 (minichromosome maintenance 2-7) complex. These six MCMs are homologous proteins that form hexameric structures, bind DNA, and have ATPase activity. MCMs are members of the AAA (ATPase associated with various cellular activities) family and have been implicated in replication fork stability and genomic integrity. Much remains to be discovered about the exact role of MCMs in the DNA copying process.

Dr. Megan Davey in the Department of Biochemistry at the University of Western Ontario studied the mechanisms underlying DNA replication. She focused on the protein machinery involved in the initiation of replication, namely, protein complexes that assemble at replication forks. Her research examined the mechanisms by which the MCM2-7 complex and associated proteins 1) load onto DNA origins during the initiation of replication; 2) become activated prior to DNA unwinding during replication; and 3) unwind DNA during replication. Dr. Davey’s research on DNA replication was critical for revealing the inner workings of nature’s photocopier in normal cells, as well as in certain diseased states in which replicative proteins are defective, such as in some cancers.

To explore the protein complexes involved in the initiation of replication, Dr. Davey used yeast as a model system, as well as molecular genetics, molecular biology, and in vitro functional assays. She tested purified recombinant proteins (wild type and mutated forms of replicative proteins) for enzymatic activity, DNA-binding and DNA-unwinding abilities, and interactions with other proteins.

Through advances in technology, we continue to develop more efficient copying techniques. Nature, however, has already perfected the ultimate copying machine of DNA replication, and Dr. Davey continued to unravel its secrets.

This research was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC), Canada Foundation for Innovation (CFI), Ontario Innovation Trust (OIT), and the University of Western Ontario.

Publications

How we remember Megan...

"Encouragement for students."

- Ran Wei (Biochemistry graduate student, Western University)

"Megan always approached teaching and training her students with great enthusiasm. Her passion for science inspired her students to excel. I remember her caring nature went so far as to help me out with an experiment at 1 o'clock in the morning! She went well above and beyond to help others and even when facing difficult times, her concern was always for others. I, and all of her students, are forever grateful for her sharing her wisdom with us and her support. Her inspirations will certainly carry on with her students."

- Dr. Brent Stead (1st PhD student to graduate from Davey lab)

"I was a post-doctoral fellow in Mike O'Donnell's laboratory at about the same time as Megan, and we shared wonderful times together. I appreciated her cheerful and strong personality and her effortlessly pragmatic approach to everything. She helped make Mike's laboratory a fabulously fun place to work in. I could attribute at least one round of laughter each day to her quirky, sharp sense of humour and quick wit. Also, her deep love of science inspired me often and reaffirmed my dedication to an academic career, for which I remain deeply grateful. Her spirit will remain with me for a long time to come."

- Manju Hingorani (former post-doc in Dr. Mike O'Donnell's lab at Rockefeller University, NY; now Associate Professor at Wesleyan University, CT)

"I got to know Megan mainly through scientific conferences, since, like her, I work on DNA replication. The first time I met her, she was just months away from starting up her own lab, and already it was clear from her success as a researcher and her infectious enthusiasm for science that she would make a first rate group leader.

"Over the years, we saw each other many times, and even held joint lab meetings on occasion. I was always happy to find out that she would be attending the same meeting as me, not only because I looked forward to hearing her latest findings, and greatly valued the feedback she provided on the research from my lab, but because she was such a friendly, humorous and empathetic person.

"Megan’s numerous triumphs in the face of adversity over the past few years are nothing short of inspirational. It was great to see her this past May during a symposium at Western, fresh from a string of high quality publications from her lab, and success in obtaining two major grants. I said to her then that she had set a high bar for the rest of us to aspire to.

"We can all be grateful to Megan for the significant progress she made in uncovering the mechanisms governing cell division, and for her generosity as a colleague, mentor and friend. She will be greatly missed."

- Bernard Duncker (Associate Professor, Dept. of Biology, University of Waterloo)

"I will remember her strength and courage in the face of adversity, her sense of humour (motto: Keep Calm and Carry On), and her stories about her dog, Oreo."

- Lynn Weir (Biochemistry Dept., Western University)