Home » Uncategorized » New Manuscript Published: Selective base excision repair of DNA damage by the non‐base‐flipping DNA glycosylase AlkC.

New Manuscript Published: Selective base excision repair of DNA damage by the non‐base‐flipping DNA glycosylase AlkC.

New Manuscript Published: Selective base excision repair of DNA damage by the non‐base‐flipping DNA glycosylase AlkC.

The preservation of genomic integrity performed by DNA repair machinery is crucial for living organisms, and malfunctions in DNA repair machinery can have far-reaching and devastating effects on a cell’s ability to attain precise DNA replication, properly regulate cell differentiation and self-renewal, and to regulate cell growth and apoptosis, among other important cellular functions. Mutations of critical residues in DNA repair proteins can drastically reduce DNA repair capability in cells, allowing for a build-up of genomic mutations. Inherited variants in DNA repair proteins such as glycosylase MUTYH have been linked to a predisposition to tumors in patients with disease MUTYH Associated Polyposis (MAP). The David Lab is interested in delineating DNA repair mechanisms to help shed light on the etiology of cancer and other diseases, providing mechanistic and structural information that may be used, for example, to design drug molecules targeting DNA repair proteins.

New work from the David Lab examined the selective base excision repair of DNA damage by the non-base-flipping DNA glycosylase AlkC, which primarily targets alkylated-DNA damage product N3-methyladenine (3mA). This work details how AlkC selects for and excises 3mA with its non-base-flipping mechanism. The authors carried out a comprehensive phylogenetic, biochemical, and structural comparison of AlkC and AlkD proteins for comparison, which shows, notably, characteristics important for substrate specificity and why bulkier substrates are not preferred. Interestingly, AlkC’s excision mechanism involves using HEAT-like repeat domains and in most cases Ig-like domains to introduce a kink in the target DNA, helping to expose the target nucleobase, allowing for subsequent insertion of the enzyme active site to excise its target.

Click here to read more about AlkC’s non-base-flipping mechanism.

 

Source:

The EMBO Journal 

 

RSS Science Daily News

  • Galactic mystery: Why massive stars struggle to form in the Milky Way’s center June 15, 2025
    At the heart of our galaxy lies a cosmic puzzle: although the Galactic Center is packed with star-making material, massive stars form there surprisingly slowly. Using NASA's retired SOFIA observatory, scientists captured rare high-resolution infrared views that revealed dozens of new stars being born, but not in the numbers or sizes one might expect.
  • Passive cooling breakthrough could slash data center energy use June 14, 2025
    UC San Diego engineers have created a passive evaporative cooling membrane that could dramatically slash energy use in data centers. As demand for AI and cloud computing soars, traditional cooling systems struggle to keep up efficiently. This innovative fiber membrane uses capillary action to evaporate liquid and draw heat away without fans or pumps. It […]
  • Why giant planets might form faster than we thought June 14, 2025
    Astronomers using ALMA have uncovered how gas and dust in planet-forming disks evolve separately an insight that reshapes our understanding of how different types of planets form. While dust lingers, gas dissipates quickly, narrowing the window for the formation of gas giants like Jupiter.
  • CRISPR-edited stem cells reveal hidden causes of autism June 14, 2025
    A team at Kobe University has created a game-changing resource for autism research: 63 mouse embryonic stem cell lines, each carrying a genetic mutation strongly associated with the disorder. By pairing classic stem cell manipulation with precise CRISPR gene editing, they ve built a standardized platform that mirrors autism-linked genetic conditions in mice. These models […]
  • Africa's pangolin crisis: The delicacy that's driving a species to the brink June 14, 2025
    Study suggests that appetite for bushmeat -- rather than black market for scales to use in traditional Chinese medicine -- is driving West Africa's illegal hunting of one of the world's most threatened mammals. Interviews with hundreds of hunters show pangolins overwhelmingly caught for food, with majority of scales thrown away. Survey work shows pangolin […]

Contact:

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

Department of Chemistry
One Shields Ave.
Davis, CA 95616