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DR. MEGAN DAVEY

cartoon of helicase during DNA replication

 

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 Dept. of Biochemistry at the University of Western Ontario studies the mechanisms underlying DNA replication. She focuses on the protein machinery involved in the initiation of replication, namely, protein complexes that assemble at replication forks. Her research examines 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 is 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 uses yeast as a model system, as well as molecular genetics, molecular biology, and in vitro functional assays. She tests 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 will continue to unravel its secrets.

   This research is 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.

 © Lynn Weir, 2009

 

Profile for Dr. Megan Davey

 

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Dr. Megan Davey
Assistant Professor - Department of Biochemistry
MSB358 - Medical Sciences Bldg.
University of Western Ontario
London, ON
Canada  N6A 5C1

519-661-2111, ext 81414
mdavey5@uwo.ca

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Updated by Lynn Weir, Nov 2011

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