Home » Posts tagged 'Mutyh'

Tag Archives: Mutyh

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#

 

New Manuscript Published: The Zinc Linchpin Motif in the DNA Repair Glycosylase MUTYH: Identifying the Zn2+ Ligands and Roles in Damage Recognition and Repair.

New Manuscript Published: The Zinc Linchpin Motif in the DNA Repair Glycosylase MUTYH: Identifying the Zn2+ Ligands and Roles in Damage Recognition and Repair.

A recent publication from the David, Siegel and Lim (Academia Sinica, Taiwan) labs (Nuñez et al., JACS, 2018) provides insight into the coordination sphere and critical role of a Zn2+ metal binding site in the DNA repair glycosylase MUTYH. Genome database mining and sequence alignment of MUTYH orthologs, along with computational modeling, identified and supported Zn2+ ligation by four Cys residues. Three of the Cys residues lie in an interdomain connector region unique to mammalian MutY enzymes, while the 4th Cys is located in close proximity to the Fe-S cluster DNA binding domain. The functional consequences of reduced Zn2+ chelation on MUTYH-mediated DNA repair activity evaluated using a battery of in vitro and cell-based assays revealed the importance of Zn-coordination in recognition of the damaged DNA substrate. The critical nature of the “Zinc Linchpin Motif” suggests additional functions unique to higher organisms in damage signaling and crosstalk with other DNA repair pathways.

More information at https://pubs.acs.org/doi/10.1021/jacs.8b06923.

Source:

J. Am. Chem. Soc. 2018, 140, 13260-13271.

Keywords: #Muty #Mutyh #BER #DNA #DNARepair #ZincLinchpinMotif #Zn2+ #8OG #DavidLab #UCDavis

 

 

 

 

 

Just Accepted Manuscript: Structure Activity Relationships Reveal Key Features of 8-Oxoguanine:Adenine Mismatch Detection by the MutY DNA Glycosylase


7/20/2017

The recently accepted manuscript, Structure Activity Relationships Reveal Key Features of 8-Oxoguanine:Adenine Mismatch Detection by the MutY DNA Glycosylase, was accepted for publication in ACS Chemical Biology.

MutY, remarkably, is able to specifically recognize and initiate repair of target OG:A mismatches from among a vast sea of natural DNA. To help reveal molecular features of OG that are critical for MutY recognition, this work explored the effects of systematic OG:A substrate alterations on MutY recognition in a cellular context. OG analogs were synthesized, assembled into OG:A modified oligonucleotides, and structure activity relationships were investigated using binding and cellular repair assays. Read the article to find out more about how specific OG modifications effect MutY glycosylase activity. Click here for the article: http://pubs.acs.org/doi/abs/10.1021/acschembio.7b00389.

 

Keywords: #Muty #DNA #DNARepair #BER #ModifiedNucleosides #Enzymes #8OG #DavidLab #UCDavis #glycosylase

Congratulations to Doug Banda and coworkers!


5/31/2017

Congratulations to David Lab authors Doug, Nicole, Michael, and Katie on their recently released article, “Repair of 8-OXOG:A Mismatches by the MUTYH Glycosylase: Mechanisms, Metals and Medicine,” in Free Radical Biology and Medicine! The final version of the article is now available online.

Link to their new article here: https://authors.elsevier.com/a/1V8Lr3AkHAI6DS.


 

RSS Science Daily News

  • Scientists’ top 10 bee-magnet blooms—turn any lawn into a pollinator paradise July 7, 2025
    Danish and Welsh botanists sifted through 400 studies, field-tested seed mixes, and uncovered a lineup of native and exotic blooms that both thrill human eyes and lure bees and hoverflies in droves, offering ready-made recipes for transforming lawns, parks, and patios into vibrant pollinator hotspots.
  • Whispers in the womb: How cells “hear” to shape the human body July 7, 2025
    Scientists found that embryonic skin cells “whisper” through faint mechanical tugs, using the same force-sensing proteins that make our ears ultrasensitive. By syncing these micro-movements, the cells choreograph the embryo’s shape, a dance captured with AI-powered imaging and computer models. Blocking the cells’ ability to feel the whispers stalls development, hinting that life’s first instructions […]
  • Breakthrough battery lets physicists reverse entanglement—and rewrite quantum law July 7, 2025
    Scientists have finally uncovered a quantum counterpart to Carnot’s famed second law, showing that entanglement—once thought stubbornly irreversible—can be shuffled back and forth without loss if you plug in a clever “entanglement battery.”
  • How a lost gene gave the sea spider its bizarre, leggy body July 7, 2025
    Scientists have decoded the sea spider’s genome for the first time, revealing how its strangely shaped body—with organs in its legs and barely any abdomen—may be tied to a missing gene. The detailed DNA map shows this ancient creature evolved differently from its spider and scorpion cousins, lacking genome duplications seen in those species. With […]
  • Feeling mental exhaustion? These two areas of the brain may control whether people give up or persevere July 7, 2025
    When you're mentally exhausted, your brain might be doing more behind the scenes than you think. In a new study using functional MRI, researchers uncovered two key brain regions that activate when people feel cognitively fatigued—regions that appear to weigh the cost of continuing mental effort versus giving up. Surprisingly, participants needed high financial incentives […]

Contact:

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

Department of Chemistry
One Shields Ave.
Davis, CA 95616