Related Experiment Video
Updated: Aug 8, 2026
08:31
Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy
Published on: June 8, 2018
Artemis links ATM to double strand break rejoining
Penny A Jeggo1, Markus Löbrich
1Genome Damage and Stability Centre, University of Sussex, East Sussex, UK. p.a.jeggo@sussex.ac.uk
Cell Cycle (Georgetown, Tex.)
|February 3, 2005
Summary
Ataxia telangiectasia mutated protein (ATM) regulates DNA repair by controlling the Artemis nuclease. This ATM-dependent end-processing pathway is crucial for repairing DNA double-strand breaks (DSBs) and cell survival after irradiation.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Ataxia telangiectasia mutated protein (ATM) is a key kinase in DNA damage response, regulating cell cycle arrest and apoptosis.
- A-T cells exhibit unrepaired DNA double-strand breaks (DSBs) after ionizing radiation (IR), suggesting a defect in DNA repair.
- The molecular basis for this repair defect in A-T cells has remained unclear.
Purpose of the Study:
- To investigate the role of Artemis, a novel ATM substrate, in DNA double-strand break (DSB) repair.
- To elucidate the mechanism by which ATM regulates DNA end processing in response to ionizing radiation (IR).
Main Methods:
- Identified Artemis as a novel ATM substrate.
- Investigated the functional relationship between ATM and Artemis in DSB repair.
- Utilized components of the ATM signaling pathway, including Nbs1, Mre11, H2AX, and 53BP1.
Main Results:
- Artemis and ATM function in a common pathway for processing a subset of IR-induced DSBs that are rejoined slowly by non-homologous end-joining (NHEJ).
- ATM-dependent regulation of DNA end processing by Artemis is essential for DSB repair.
- This repair process significantly contributes to cell survival after irradiation.
Conclusions:
- ATM signaling controls DNA end processing via the nuclease Artemis.
- This ATM-Artemis pathway is critical for the repair of specific DSBs and subsequent cell survival post-irradiation.
- Findings reveal a new dimension of ATM's role in DNA damage response, specifically in regulating DNA end processing during cell cycle delay.
Related Concept Videos
01:02Long-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:
02:04Fixing 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...
02:36DNA 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...
02:31Homologous 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...
02:37Restarting Stalled Replication Forks
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
02:04Fixing 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...