Related Experiment Video
Updated: May 21, 2025
08:31
Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy
Published on: June 8, 2018
9.0K
Nuclear and genome dynamics underlying DNA double-strand break repair
Irene Chiolo1, Matthias Altmeyer2, Gaëlle Legube3
1Department of Molecular and Computational Biology, University of Southern California, Los Angeles, CA, USA. chiolo@usc.edu.
Nature Reviews. Molecular Cell Biology
|March 18, 2025
Summary
Nuclear architecture and genome organization are crucial for DNA repair and cell survival. Understanding these dynamics offers new therapeutic strategies for cancer and aging.
Area of Science:
- Cell Biology
- Genetics
- Biochemistry
Background:
- Nuclear shape and chromosome organization changes are observed in cancer, aging, and DNA damage.
- The precise relationship between nuclear architecture, genome organization, chromosome stability, and overall health is not fully understood.
Purpose of the Study:
- To review the dynamic mechanisms regulating nuclear and genome organization for DNA double-strand break (DSB) repair, genome stability, and cell survival.
- To explore how these processes are altered in cancer and aging.
Main Methods:
- Review of existing literature on nuclear architecture, genome dynamics, and DNA repair mechanisms.
- Analysis of studies investigating the positioning and mobility of damaged DNA within the nucleus.
Main Results:
- Genome dynamics supporting DSB repair involve chromatin states, repair condensates, cytoskeletal elements (microtubules, actin), motor proteins, the nuclear envelope, and nuclear compartments.
- Chromosome topology and chromatin loop extrusion are key regulatory factors.
- These mechanisms are frequently dysregulated in cancer and aging.
Conclusions:
- The dynamic reshaping of the genome within nuclear space during DSB repair presents novel therapeutic targets.
- Interventions could exploit cancer cell vulnerabilities or address age-associated genomic instability.
Related Concept Videos
02:04Fixing Double-strand Breaks
11.9K
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...
11.9K
02:31Homologous Recombination
50.0K
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...
50.0K
02:25Overview of DNA Repair
29.8K
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...
Chemically...
29.8K
01:38Nucleotide Excision Repair
3.4K
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...
3.4K
02:37DNA Damage can Stall the Cell Cycle
9.0K
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...
9.0K
01:02Long-patch Base Excision Repair
6.9K
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:
6.9K