Misregulation of DNA building blocks associated with the development of colon cancer

Misregulation of DNA building blocks associated with the development of colon cancer
Professor Andrei Chabes is one of the researchers at Umeå University in Sweden behind the new findings. Credit: Mattias Pettersson, Umeå University

When cells divide, the proper balance between the four DNA building blocks is required in order for the DNA to be copied without the introduction of potentially harmful mutations. Researchers at Umeå University in Sweden have now shown a connection between levels of DNA building blocks - dNTPs - and colon cancer. This discovery has been published in the Proceedings of the National Academy of Sciences.

"Together with other researchers, we have previously shown that small changes in the levels of DNA building blocks increase the mutation rates in ," says Professor Andrei Chabes, one of the researchers at Umeå University behind the new findings. "This is what got us interested in studying the proteins involved in the regulation of dNTP in . Our objective was to identify mutations that affect dNTP levels and thus increase the in cancer cells."

The Umeå-based research team found that the protein SAMHD1, which is involved in the break-down of dNTP, is often mutated in cells. Further studies in mice, yeast, and cultures of human cells showed that these cancer-specific mutations eliminated the SAMHD1 function and that this led to an elevation and imbalance in dNTP levels and hence an increased mutation rate.

"What's so remarkable about our observation is that even if only one of the two SAMHD1 gene copies is lost, it affects dNTP levels with an increased mutation rate as a result. Together with a deficiency in the protein MLH1, which is involved in the correction of mutations and is often mutated in colon cancers, we can see a huge increase in the number of emerging mutations," explains Professor Andrei Chabes.

The new results have been published in the highly acclaimed journal Proceedings of the National Academy of Sciences. The researchers have reason to believe that the results will lead to other similar discoveries - both in other cancers and in other proteins involved in dNTP synthesis.

"SAMHD1 is only one of several dozen proteins involved in the regulation of dNTPs. In theory, a change in function in any of these proteins can affect dNTP levels. We are merely showing the principle. It now remains to be seen how changes in dNTP levels affect the development of colon cancer and if changes in dNTP levels occur in other cancers," says Professor Andrei Chabes.


Explore further

Mutations in gene SETD2 make cancer cells vulnerable to drug inhibiting the protein WEE1

More information: Matilda Rentoft et al. Heterozygous colon cancer-associated mutations of have functional significance , Proceedings of the National Academy of Sciences (). DOI: 10.1073/pnas.1519128113
Provided by Umea University
Citation: Misregulation of DNA building blocks associated with the development of colon cancer (2016, April 12) retrieved 19 September 2019 from https://medicalxpress.com/news/2016-04-misregulation-dna-blocks-colon-cancer.html
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
62 shares

Feedback to editors

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more