Related Experiment Video

Updated: Feb 15, 2026

Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates
06:10

Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates

Published on: May 9, 2025

979

Restoration of ATM Expression in DNA-PKcs-Deficient Cells Inhibits Signal End Joining

Jessica A Neal1, Yao Xu1, Masumi Abe2

  • 1Department of Microbiology and Molecular Genetics, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824; Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824;

Journal of Immunology (Baltimore, Md. : 1950)
|February 28, 2016
PubMed

Insights

Targeted deletion of DNA-PKcs abrogates VDJ signal end joining. ATM expression impacts this process differently depending on DNA-PKcs deficiency, suggesting ATM restricts signal ends to nonhomologous end joining.

Area of Science:

  • Molecular Biology
  • Immunology
  • Genetics

Background:

  • DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) is crucial for DNA repair.
  • DNA-PKcs deficiency often leads to reduced ATM expression.
  • The interplay between DNA-PKcs and ATM in VDJ recombination is not fully understood.

Purpose of the Study:

  • To investigate the impact of DNA-PKcs and ATM loss on VDJ signal end joining.
  • To explore how varying ATM expression levels influence VDJ recombination in different cell lines.
  • To elucidate the role of ATM in directing signal ends to specific DNA repair pathways.

Main Methods:

  • Targeted deletion of DNA-PKcs in human cell lines.
  • Episomal VDJ signal end joining assays.
  • Analysis of ATM expression in DNA-PKcs-deficient cells and mice.
  • Investigating VDJ recombination in human and rodent cell strains with varying ATM and DNA-PKcs levels.

Main Results:

  • DNA-PKcs deletion abrogated VDJ signal end joining in human cells.
  • Restoration of ATM in DNA-PKcs-deficient mouse cells proficient in signal end joining inhibited the process.
  • Loss of ATM in DNA-PKcs-deficient cells deficient in signal end joining enhanced signal joint formation.

Conclusions:

  • ATM plays a regulatory role in VDJ signal end joining.
  • ATM appears to facilitate the restriction of signal ends to the classical nonhomologous end-joining pathway.
  • The interaction between DNA-PKcs and ATM is complex and context-dependent in VDJ recombination.

More Related Videos

Author Spotlight: Investigating the Potential of Chinese Herbal Medicinal Active Dioscin in Treating IgA Nephropathy14:18

Author Spotlight: Investigating the Potential of Chinese Herbal Medicinal Active Dioscin in Treating IgA Nephropathy

Published on: October 13, 2023

1.8K
CRISPR/Cas9 Technology in Restoring Dystrophin Expression in iPSC-Derived Muscle Progenitors07:44

CRISPR/Cas9 Technology in Restoring Dystrophin Expression in iPSC-Derived Muscle Progenitors

Published on: September 14, 2019

8.9K

Related Concept Videos

What is Cell Signaling?02:03

What is Cell Signaling?

Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate to respond to the environment.
131.2K
Restorative Care01:19

Restorative Care

Restorative care is provided once a patient has been discharged from a healthcare facility and requires additional services. The additional services include home care, rehabilitation programs, and extended care. Restorative care centers help the patient regain their previous level of functioning or acquire a new level of functioning due to the incapacitating effects of a disease or a disability. It aims to assist patients in enhancing their quality of life by encouraging independence,...
2.4K
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
26.6K
DNA-only Transposons02:57

DNA-only Transposons

DNA-only transposons are called autonomous transposons since they code for the enzyme transposase that is required for the transposition mechanism. Insertion of transposons can alter gene functions in multiple ways. They can mutate the gene, alter gene expression by introducing a novel promoter or insulator sequence, introduce new splice sites, and change the mRNA transcripts produced, or remodel chromatin structure.
The donor site from where the transposon is excised is either degraded or...
17.6K
What is Gene Expression?01:42

What is Gene Expression?

Overview
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
197.2K
Feedback Inhibition00:46

Feedback Inhibition

Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!
57.4K