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DNA Electrochemistry Shows DNMT1 Methyltransferase Hyperactivity in Colorectal Tumors

Furst, Ariel L. and Barton, Jacqueline K. (2015) DNA Electrochemistry Shows DNMT1 Methyltransferase Hyperactivity in Colorectal Tumors. Chemistry and Biology, 22 (7). pp. 938-945. ISSN 1074-5521. PMCID PMC4518711. https://resolver.caltech.edu/CaltechAUTHORS:20150625-120207586

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.chembiol.2015.05.019DOIArticle
http://www.sciencedirect.com/science/MiamiMultiMediaURL/1-s2.0-S1074552115002094/1-s2.0-S1074552115002094-mmc1.pdf/272022/html/S1074552115002094/986a4773e678aea81ae16f53390a591e/mmc1.pdfPublisherSupplemental Information
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518711PubMed CentralArticle
ORCID:
AuthorORCID
Barton, Jacqueline K.0000-0001-9883-1600
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.
Funders:
Funding AgencyGrant Number
NIHGM61077
Issue or Number:7
PubMed Central ID:PMC4518711
Record Number:CaltechAUTHORS:20150625-120207586
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150625-120207586
Official Citation:Ariel L. Furst, Jacqueline K. Barton, DNA Electrochemistry Shows DNMT1 Methyltransferase Hyperactivity in Colorectal Tumors, Chemistry & Biology, Volume 22, Issue 7, 23 July 2015, Pages 938-945, ISSN 1074-5521, http://dx.doi.org/10.1016/j.chembiol.2015.05.019. (http://www.sciencedirect.com/science/article/pii/S1074552115002094)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:58609
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:25 Jun 2015 19:39
Last Modified:27 Apr 2020 23:09

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