Related Experiment Video
Updated: Jul 11, 2025
10:59
Atomic Force Microscopy Investigations of DNA Lesion Recognition in Nucleotide Excision Repair
Published on: May 24, 2017
9.5K
Structural and biochemical insights into NEIL2's preference for abasic sites
Brian E Eckenroth1, Joshua D Bumgarner2, Olivia Matsumoto-Elliott2
1Department of Microbiology and Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405, USA.
Nucleic Acids Research
|November 16, 2023
Summary
Mammalian NEIL2 glycosylase repairs oxidative DNA damage. Its structure reveals conformational changes upon binding abasic sites, highlighting its lyase activity for DNA repair.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Cellular DNA repair is crucial for genomic stability.
- Base excision repair (BER) pathway utilizes DNA glycosylases to remove damaged bases.
- NEIL2 is a mammalian DNA glycosylase involved in repairing oxidative DNA damage.
Purpose of the Study:
- To determine the crystal structure of mammalian NEIL2 bound to DNA.
- To elucidate the structural mechanisms of NEIL2 in DNA repair.
- To understand NEIL2's substrate specificity and enzymatic activity.
Main Methods:
- X-ray crystallography at 2.08 Å resolution.
- Biochemical analysis of NEIL2 activity.
- Structural comparison of liganded and unliganded NEIL2.
Main Results:
- The first liganded crystal structure of NEIL2 complexed with an abasic site analog DNA duplex was determined.
- Binding induced significant interdomain conformational shifts and local changes in NEIL2.
- Biochemical data revealed NEIL2's preference for lyase activity on oxidized bases and abasic sites.
Conclusions:
- NEIL2 undergoes substantial conformational changes upon DNA binding to facilitate repair.
- The structural and biochemical data provide insights into NEIL2's mechanism of action.
- Understanding NEIL2's function is vital for interpreting the biological impact of genetic variants.
More Related Videos
Related Concept Videos
01:02Long-patch Base Excision Repair
7.0K
Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
7.0K
01:28Biosynthesis of Nucleic Acids
54
Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
54
01:11Restriction Enzymes
30.7K
Restriction enzymes are bacterial enzymes used to cut DNA in a sequence-specific manner. To cleave DNA, they bind to specific palindromic sequences called restriction sites. Such palindromic DNA sequences or inverted repeats are commonly found in regions of functional significance, such as the origin of replication, gene operator sites, and regions containing transcription termination signals.
The host bacteria protect their own genomic DNA from these enzymes by methylating these sites. Some...
The host bacteria protect their own genomic DNA from these enzymes by methylating these sites. Some...
30.7K
01:38Nucleotide Excision Repair
3.5K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.5K
01:54Base Excision Repair
22.4K
One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...
The first step of...
22.4K
01:49Conserved Binding Sites
4.2K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.2K