Home » News » Recent Article Published: Unique H-bonding of Adenine with oxidatively damaged base 8-oxoguanosine enables specific recognition and repair by DNA glycosylase MutY.

Recent Article Published: Unique H-bonding of Adenine with oxidatively damaged base 8-oxoguanosine enables specific recognition and repair by DNA glycosylase MutY.

Recent Article Published by Sheila David’s Lab: Unique Hydrogen Bonding of Adenine with the Oxidatively Damaged Base 8-Oxoguanine Enables Specific Recognition and Repair by DNA Glycosylase MutY.

Majumdar, C.; Mckibbin, P.L.; Krajewski, A.E.; Manlove, A.H.; Lee, J.K.; David, S.S.
J. Am. Soc. 2020. 142, 48, 20340–20350.

      DNA repair protein MutY employs specific interactions to differentiate OG:A basepairs from canonical G:C and T:A basepairs. Prior work from our lab has focused on understanding the structural requirements of OG on lesion recognition and catalysis, and we have shown that MutY relies on the exocyclic 2-amino group of OG to identify and distinguish OG:A from other basepairs. Additionally, we’ve shown that OG binding induces conformational changes that influence A excision.

     This new work uses structure-activity relationships (SARs) to identify the structural features of A that influence OG:A recognition, verification, base excision, and overall cellular repair. We correlate observed in vitro MutY activity on A analogue substrates with their experimental and calculated acidities to provide mechanistic insight into the factors influencing MutY base excision efficiency. Our results herein can be used to guide future design of MutY/MUTYH specific probes to monitor the activity, or lack thereof, of MutY/MUTYH variants. These results can also applied toward the development of MUTY/MUTYH specific inhibitors that may find utility in cancer therapeutics.

Click on the link or graphical abstract to find out more!

https://pubs.acs.org/doi/abs/10.1021/jacs.0c06767#

 

RSS Science Daily News

  • Composition of asteroid Phaethon November 28, 2023
    Asteroid Phaethon, which is five kilometers in diameter, has been puzzling researchers for a long time. A comet-like tail is visible for a few days when the asteroid passes closest to the Sun during its orbit. However, the tails of comets are usually formed by vaporizing ice and carbon dioxide, which cannot explain this tail. […]
  • How shifting climates may have shaped early elephants' trunks November 28, 2023
    Researchers have provided new insights into how ancestral elephants developed their dextrous trunks.  A study of the evolution of longirostrine gomphotheres, an ancestor of the modern day elephant, suggests moving into open-land grazing helped develop their coiling and grasping trunks.
  • What if Alexa or Siri sounded more like you? Study says you'll like it better November 28, 2023
    One voice does not fit all when it comes to virtual assistants like Siri and Alexa, according to researchers who examined how customization and perceived similarity between user and voice assistant (VA) personalities affect user experience. They found a strong preference for extroverted VAs -- those that speak louder, faster and in a lower pitch. […]
  • A gamma-ray pulsar milestone inspires innovative astrophysics and applications November 28, 2023
    Scientists have announced the discovery of nearly 300 gamma ray pulsars.
  • Solar activity likely to peak next year November 28, 2023
    Researchers have discovered a new relationship between the Sun's magnetic field and its sunspot cycle, that can help predict when the peak in solar activity will occur. Their work indicates that the maximum intensity of solar cycle 25, the ongoing sunspot cycle, is imminent and likely to occur within a year.

Contact:

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

Department of Chemistry
One Shields Ave.
Davis, CA 95616