Related Experiment Video

Updated: Oct 26, 2025

Assessment of Global DNA Double-Strand End Resection using BrdU-DNA Labeling coupled with Cell Cycle Discrimination Imaging
06:44

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

Published on: April 28, 2021

4.2K

Understanding the DNA double-strand break repair and its therapeutic implications

Ujjayinee Ray1, Sathees C Raghavan1

  • 1Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.

DNA Repair
|July 29, 2021
PubMed

Insights

Targeting DNA double-strand break (DSB) repair pathways with small molecule inhibitors shows promise for cancer therapy. Molecular profiling of repair proteins can improve patient outcomes when combined with existing treatments.

Area of Science:

  • Molecular Biology
  • Cancer Therapeutics
  • Genetics

Background:

  • DNA double-strand breaks (DSBs) are critical DNA lesions repaired by homologous recombination, nonhomologous end joining, and microhomology-mediated end joining.
  • Targeting these DSB repair pathways with small molecule inhibitors offers a strategy to enhance cancer treatment efficacy, particularly in tumors with altered repair mechanisms.

Purpose of the Study:

  • To review the mechanisms of DSB repair and chromatin dynamics.
  • To discuss the modulation of small molecule inhibitors in cancer therapy.
  • To explore the integration of molecular profiling with current cancer treatment modalities.

Main Methods:

  • Review of existing literature on DNA double-strand break repair pathways.
  • Analysis of small molecule inhibitors targeting DSB repair proteins.
  • Discussion of chromatin dynamics in DNA repair accessibility.
  • Integration of molecular profiling with therapeutic strategies.

Main Results:

  • Small molecule inhibitors targeting DSB repair pathways can sensitize tumors to radio and chemotherapy.
  • While several inhibitors are in clinical trials, only PARP inhibitors (targeting single-strand break repair) are approved.
  • Molecular profiling of repair proteins can guide prognostic and therapeutic decisions.

Conclusions:

  • Targeting DSB repair pathways is a promising strategy for cancer treatment.
  • Further development of small molecule inhibitors and integration with molecular profiling are warranted.
  • Combination therapy with existing treatments and personalized approaches can improve patient outcomes.
Keywords:
Cancer therapyChromatin accessibilityDSB repairDouble-strand breakGenomic instabilityHomologous recombinationMMEJMicrohomology mediated end joiningNHEJNonhomologous DNA end joining

More Related Videos

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy08:31

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy

Published on: June 8, 2018

9.3K
Using Next Generation Sequencing to Identify Mutations Associated with Repair of a CAS9-induced Double Strand Break Near the CD4 Promoter06:59

Using Next Generation Sequencing to Identify Mutations Associated with Repair of a CAS9-induced Double Strand Break Near the CD4 Promoter

Published on: March 31, 2022

2.6K

Related Concept Videos

Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
13.2K
Fixing Double-strand Breaks02:04

Fixing Double-strand Breaks

3.6K
Homologous Recombination02:31

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
56.6K
Overview of DNA Repair02:25

Overview of DNA Repair

In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
32.3K
Overview of DNA Repair02:25

Overview of DNA Repair

8.4K
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:
7.3K