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The David Lab at UC Davis utilizes numerous tools of chemical biology to explore the complex mechanistic details of DNA repair enzymes. DNA repair proteins such as MutY and NEIL, among the targets of research of the David Lab, help catalyze necessary repair of oxidative DNA damage, and are critical to maintaining genomic integrity in organisms living in the oxygen-rich environment of Earth. The David Lab is headed by Dr. Sheila S. David, who has led at the forefront of DNA repair research for over 25 years. The David Lab continues to push forward the world’s current understanding of DNA repair enzymes by leveraging our unique expertise in DNA repair enzymology while venturing into new areas and collaborating with scientists around the world.

Featured Article: 

The DNA repair enzyme MUTYH potentiates cytotoxicity of the alkylating agent MNNG by interacting with abasic sites

Journal of Biological Chemistry

Inherited defects in the DNA repair gene MUTYH lead to cancer, proof that MUTYH has a critical role in preventing cancer in normal cells. In a new study from the David Lab, MUTYH is shown to have a new role that implicates it in the response to a common class of chemotherapy drugs, alkylating agents (https://www.jbc.org/content/early/2020/01/30/jbc.RA119.010497).

 

Cancer cells evolve resistance to chemotherapy drugs by a number of mechanisms, including upregulating DNA repair enzymes such as BRCA1, which helps cancer cells survive DNA damaging chemotherapy agents. Surprisingly, MUTYH does not help repair alkylating agent DNA damage, but instead enhance alkylating agent toxicity. This study uncovers the underlying molecular mechanism of this activity, which involves MUTYH stimulating cells to create more toxic DNA repair intermediates. By uncovering the molecular mechanism, this research suggests that MUTYH has both a role in preventing DNA mutations that cause cancer, and a separate role in helping kill cancer cells that are treated with chemotherapy drugs, thus the loss of MUTYH is a “double-whammy”. Tests to determine if cancer patients have normal versus functionally-deficient MUTYH may alter chemotherapy treatment choices if these results can be generalized to clinical practice.

Raetz, A.G.; Banda, D.M.; Ma, X.; Xu, G.; Rajavel, A.N.; McKibbin, P.L.; Lebrilla, C.B.; David, S.S. The DNA repair enzyme MUTYH potentiates cytotoxicity of the alkylating agent MNNG by interacting with abasic sites. J. Biol. Chem. 2020.

doi: 10.1074/jbc.RA119.010497

 

Recent Articles:

Featured Photos:

ACS Chemical Biology LiveSlides Presentation: 

Structure–Activity Relationships Reveal Key Features of 8-Oxoguanine: A Mismatch Detection by the MutY Glycosylase

Listen in while Chandrima Majumdar explains this recent work from the David Lab, which was selected as an ACS Editor’s Choice article.

For the latest David Lab updates, check out the News section.

Click on Research for an overview of The David Lab’s research.

A thorough list of publications is available in the Publications section. t the News section.

Click on Research for an overview of The David Lab’s research.

A thorough list of publications is available in the Publications section.

Research in the David Lab:

Graduate Student Spotlight

Introducing the David Lab Graduate Student Spotlight! Check out our conversation with Nicole as she discusses her journey as a Ph.D. student working in the David Lab.

 

Undergraduate Student Spotlight

Meet UC Davis Undergraduate Researcher Madeline Bright in our lab’s new Undergraduate Student Spotlight Video!

David Lab FYI Video

How to efficiently pour column fractions: Run a column <60 min.

Doing this will greatly increase your already-existing love of columns. And your productivity.

Get the most out of your flash column. It’s not called slow column chromatography.

Use this information at your own risk. This video is intended for graduate / professional level researchers. Be sure to follow your lab’s safety protocols.

Video by Robert Van Ostrand.

David Lab YouTube Trailer – June 2020

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David Lab Members

The David Lab – April 2019

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Keywords: #DavidLab #TheDavidLab #UCDavis #DNA #DNARepair #Muty #Mutyh #8OG #enzymes #ModifiedOligonucleotides #ModifiedNucleosides #OrganicSynthesis #Synthesis #BaseExcisionRepair #BER #NEIL #ChemicalBiology #Chemistry #SheilaDavid #UCDavisChemistry #glycosylase #DNARepairUCDavis

 

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Contact:

Dr. Sheila S. David
ssdavid@ucdavis.edu
(530)-752-4280

Department of Chemistry
One Shields Ave.
Davis, CA 95616