Related Experiment Video

Updated: Aug 20, 2026

Application of Stopped-flow Kinetics Methods to Investigate the Mechanism of Action of a DNA Repair Protein
11:01

Application of Stopped-flow Kinetics Methods to Investigate the Mechanism of Action of a DNA Repair Protein

Published on: March 31, 2010

Tumor suppressor APC blocks DNA polymerase beta-dependent strand displacement synthesis during long patch but not

Satya Narayan1, Aruna S Jaiswal, Ramesh Balusu

  • 1Department of Anatomy and Cell Biology and Shands Cancer Center, University of Florida, Gainesville, Florida 32610, USA. snarayan@ufscc.ufl.edu

The Journal of Biological Chemistry
|November 19, 2004
PubMed

Insights

The tumor suppressor protein APC regulates DNA repair pathways. This finding reveals APC

Area of Science:

  • Molecular Biology
  • Cancer Research
  • DNA Repair Mechanisms

Background:

  • The tumor suppressor protein Adenomatous Polyposis Coli (APC) is crucial in cellular processes.
  • Base Excision Repair (BER) is a key DNA repair pathway.
  • Dysregulation of BER is implicated in various cancers.

Purpose of the Study:

  • To investigate a novel role of APC in regulating DNA repair.
  • To elucidate the mechanism by which APC influences BER pathway choice.

Main Methods:

  • Identification of an APC protein domain interacting with DNA polymerase beta.
  • Assessing the impact of APC on strand-displacement synthesis in long-patch BER.
  • Utilizing colon cancer cell lines with wild-type and mutant APC.
  • Employing RNA interference to study gene expression effects.

Main Results:

  • A specific sequence in APC binds DNA polymerase beta, inhibiting long-patch BER.
  • Wild-type APC expression enhances sensitivity to DNA-methylating agents via impaired long-patch BER.
  • APC's role in DNA methylation-induced colon cancer cell sensitivity confirmed by RNA interference.

Conclusions:

  • APC plays a critical role in directing the choice between short-patch and long-patch BER pathways.
  • APC influences colon cancer cell susceptibility to carcinogens and chemotherapeutics.
  • This discovery offers new insights into APC's function in cancer development and treatment.

More Related Videos

Assessment of DNA Double Strand Break Repair Activity Using High-throughput and Quantitative Luminescence-Based Reporter Assays05:01

Assessment of DNA Double Strand Break Repair Activity Using High-throughput and Quantitative Luminescence-Based Reporter Assays

Published on: June 14, 2024

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging06:44

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging

Published on: April 28, 2021

Related Concept Videos

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:
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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...
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview