Related Experiment Video

Updated: Dec 31, 2025

ACT1-CUP1 Assays Determine the Substrate-Specific Sensitivities of Spliceosomal Mutants in Budding Yeast
07:31

ACT1-CUP1 Assays Determine the Substrate-Specific Sensitivities of Spliceosomal Mutants in Budding Yeast

Published on: June 30, 2022

2.8K

The splicing component ISY1 regulates APE1 in base excision repair

Aruna S Jaiswal1, Elizabeth A Williamson1, Gayathri Srinivasan1

  • 1Division of Hematology and Medical Oncology, Department of Medicine, University of Texas Health Science Center, San Antonio, TX 78229 United States.

DNA Repair
|December 31, 2019
PubMed

Insights

The splicing factor ISY1 enhances DNA repair by boosting apurinic/apyrimidinic endonuclease 1 (APE1) activity. This interaction is crucial for repairing oxidative DNA damage and maintaining genome stability.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Cellular genomes face constant threats from DNA damaging agents.
  • Failure to repair DNA damage can lead to replication stress and genetic instability.
  • Base excision repair (BER) is vital for removing oxidized or alkylated DNA bases, but its regulation is unclear.

Purpose of the Study:

  • To investigate the regulatory mechanisms of the Base Excision Repair (BER) pathway.
  • To identify novel factors involved in DNA damage response.
  • To elucidate the role of splicing factor ISY1 in BER.

Main Methods:

  • Investigated the interaction between ISY1 and apurinic/apyrimidinic endonuclease 1 (APE1).
  • Assessed the effect of ISY1 on APE1's 5'-3' endonuclease activity using purified recombinant proteins.
  • Reconstituted Base Excision Repair (BER) pathways in vitro to evaluate ISY1's impact.
  • Examined ISY1 expression levels in response to oxidative DNA damage.

Main Results:

  • ISY1 enhances the 5'-3' endonuclease activity of APE1.
  • ISY1 expression is induced by oxidative damage, suggesting rapid BER enhancement.
  • ISY1 and APE1 physically interact, with ISY1 improving APE1's recognition of abasic sites.
  • ISY1 significantly boosts APE1 activity in both short- and long-patch BER pathways.

Conclusions:

  • ISY1 acts as a novel regulator of the Base Excision Repair (BER) pathway.
  • The ISY1-APE1 interaction is physiologically relevant, especially when APE1 levels are suboptimal.
  • This study links pre-mRNA splicing machinery to DNA damage repair processes.
Keywords:
AP Endonuclease-1Base excision repairISY1Oxidative stressRNA splicing

More Related Videos

A Reporter Based Cellular Assay for Monitoring Splicing Efficiency08:53

A Reporter Based Cellular Assay for Monitoring Splicing Efficiency

Published on: September 15, 2021

3.1K
Using the E1A Minigene Tool to Study mRNA Splicing Changes10:25

Using the E1A Minigene Tool to Study mRNA Splicing Changes

Published on: April 22, 2021

5.3K

Related Concept Videos

RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
60.1K
Base Excision Repair01:54

Base Excision Repair

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...
25.8K
Base Excision Repair01:54

Base Excision Repair

4.9K
Nucleotide Excision Repair01:38

Nucleotide Excision Repair

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...
4.9K
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
40.5K
Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

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:
7.7K