23 Feb Genetic Defect in DNA Repair Enzyme Linked to Prostate Cancer

MedicalResearch.com Interview with:
G. Andrés Cisneros, Ph.D.
Associate Professor
Department of Chemistry Center for Advanced Scientific Computing and Modeling, University of North Texas

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The accurate maintenance of DNA is crucial, if DNA damage is not addressed it can lead to various diseases including cancer. Therefore, the question arises about what happens if enzymes in charge of DNA repair are themselves mutated. We previously developed a method to perform targeted searches for cancer-related SNPs on genes of interest called HyDn-SNP-S. This method was applied to find prostate-cancer SNPs on DNA dealkylases in the ALKB family of enzymes.

Our results uncovered a particular mutation on ALKBH7, R191Q, that is significantly associated with prostate cancer. Subsequent computer simulations and experiments indicate that this cancer mutation results in a decreased ability of ALKBH7 to bind its co-factor, thus impeding its ability to perform its native function.

MedicalResearch.com: What should readers take away from your report?

Response: It is known that DNA repair pathways can be linked to cancer. This study provides a link between a prostate-cancer mutation and DNA dealkylase ALKBH7 and provides clues as to how the mutation impacts the resulting cancer variant’s function.

This manuscript also shows how significant insights can be gained by combining computational simulations and experiments.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: This is only the beginning of the story and there is a lot of work to do to confirm the role of this mutation in prostate cancer. In addition, it would be very interesting to pursue this mutation to investigate possible new ways to detect and/or treat this disease.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation: PLOS Computational Biology

ALKBH7 Variant Related to Prostate Cancer Exhibits Altered Substrate Binding

Alice R. Walker,Pavel Silvestrov,Tina A. Müller,Robert H. Podolsky,Gregory Dyson,Robert P. Hausinger,Gerardo Andrés Cisneros
Published: February 23, 2017
http://dx.doi.org/10.1371/journal.pcbi.1005345

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Last Updated on February 23, 2017 by Marie Benz MD FAAD