DNA Electrochemistry Shows DNMT1 Methyltransferase Hyperactivity in Colorectal Tumors
- Creators
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Furst, Ariel L.
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Barton, Jacqueline K.
Abstract
DNMT1, the most abundant human methyltransferase, is responsible for translating the correct methylation pattern during DNA replication, and aberrant methylation by DNMT1 has been linked to tumorigenesis. We have developed a sensitive signal-on electrochemical assay for the measurement of DNMT1 activity in crude tissue lysates. We have further analyzed ten tumor sets and have found a direct correlation between DNMT1 hyperactivity and tumorous tissue. In the majority of samples analyzed, the tumorous tissue has significantly higher DNMT1 activity than the healthy adjacent tissue. No such correlation is observed in measurements of DNMT1 expression by qPCR, DNMT1 protein abundance by western blotting, or DNMT1 activity using a radiometric DNA labeling assay. DNMT1 hyperactivity can result from both protein overexpression and enzyme hyperactivity. DNMT1 activity measured electrochemically provides a direct measure of activity in cell lysates and, as a result, provides a sensitive and early indication of cancerous transformation.
Additional Information
© 2015 Elsevier. Received: April 23, 2015; Revised: May 27, 2015; Accepted: May 31, 2015; Published: June 25, 2015. We are grateful to the NIH (GM61077) for their financial support of this research. We also thank Prof. Michael G. Hill who provided expertise and insight that assisted the research. Author Contributions: A.L.F. conceived experiments, acquired and analyzed data, and wrote the manuscript. J.K.B. conceived experiments and wrote the manuscript.Attached Files
Accepted Version - nihms700401.pdf
Supplemental Material - mmc1.pdf
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Additional details
- PMCID
- PMC4518711
- Eprint ID
- 58609
- Resolver ID
- CaltechAUTHORS:20150625-120207586
- GM61077
- NIH
- Created
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2015-06-25Created from EPrint's datestamp field
- Updated
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2022-06-01Created from EPrint's last_modified field