Home » Uncategorized » Recent Article Published by the David Lab: The DNA repair enzyme MUTYH potentiates cytotoxicity of the alkylating agent MNNG by interacting with abasic sites.

Recent Article Published by the David Lab: The DNA repair enzyme MUTYH potentiates cytotoxicity of the alkylating agent MNNG by interacting with abasic sites.

By in Uncategorized on .

Recent Article Published by the David Lab at UC Davis:

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. 

Citation:

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

Keywords:

#sheiladavid #davidlab #mutyh #thedavidlab #ucdavischemistry #cytotoxicity #alkylatingagent #mnng #dna #dnarepair #muty #ucdavis #chemistry #biologicalchemistry #chembio #journalofbiologicalchemistry

RSS Science Daily News

  • Flamingos create water tornados to trap their prey May 12, 2025
    Flamingos have developed an amazing variety of techniques to create swirls and eddies in the water to concentrate and eat brine shrimp and other organisms, a biologist found. They stomp dance to stir organisms from the bottom and concentrate them in whorls. The organisms are then drawn upward by a head jerk that forms a […]
  • From prehistoric resident to runaway pet: First tegu fossil found in the U.S. May 12, 2025
    Originally from South America, the charismatic tegu made its way to the United States via the pet trade of the 1990s. But a recent discovery shows these reptiles are no strangers to the region -- tegus were here millions of years before their modern relatives arrived in pet carriers.
  • Submarine robot catches an underwater wave May 12, 2025
    Engineers have taught a simple submarine robot to take advantage of turbulent forces to propel itself through water.
  • Drug to slow Alzheimer's well tolerated outside of clinical trial setting May 12, 2025
    In a recent study, researchers found adverse events were rare and manageable among clinic patients with very mild or mild Alzheimer's disease who received lecanemab infusions.
  • Universe decays faster than thought, but still takes a long time May 12, 2025
    The universe is decaying much faster than thought. This is shown by calculations of scientists on the so-called Hawking radiation. They calculate that the last stellar remnants take about 10^78 years (a 1 with 78 zeros) to perish. That is much shorter than the previously postulated 10^1100 years (a 1 with 1100 zeros).

Contact:

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

Department of Chemistry
One Shields Ave.
Davis, CA 95616