Related Experiment Video

Updated: Jun 27, 2026

Oligopeptide Competition Assay for Phosphorylation Site Determination
09:16

Oligopeptide Competition Assay for Phosphorylation Site Determination

Published on: May 18, 2017

Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo

Jeremy A Daniel1, Manuela Pellegrini, Ji-Hoon Lee

  • 1Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

The Journal of Cell Biology
|December 3, 2008
PubMed

Insights

Ataxia telangiectasia mutated (ATM) kinase autophosphorylation sites are not essential for its function in vivo. ATM-dependent DNA damage responses remain functional in mice lacking these specific phosphorylation sites.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Cellular responses to DNA double-strand breaks involve the ataxia telangiectasia mutated (ATM) kinase.
  • ATM activation, crucial for cell cycle checkpoints and DNA repair, is thought to involve autophosphorylation at specific serine residues.
  • Human studies identified serine residues 367, 1893, and 1981 as individually required for ATM activation.

Purpose of the Study:

  • To investigate the physiological necessity of ATM autophosphorylation sites for kinase function in vivo.
  • To determine if ATM autophosphorylation is required for DNA damage response pathways.

Main Methods:

  • Generation of a transgenic mouse model expressing a triple serine mutant ATM (S367/1899/1987 replaced with alanine) as the sole ATM species.
  • Assessment of ATM-dependent cellular and organismal responses to DNA damage.

Main Results:

  • Mice expressing the triple serine mutant ATM exhibited functional ATM-dependent responses.
  • Both cellular and organismal levels of DNA damage response were observed to be intact.
  • ATM autophosphorylation correlates with DNA damage-induced activation but is not essential for in vivo function.

Conclusions:

  • ATM autophosphorylation, while associated with activation, is not a prerequisite for ATM's essential functions in vivo.
  • The study demonstrates that ATM can mediate critical DNA damage responses independently of these specific autophosphorylation sites.

More Related Videos

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation15:05

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

Visualizing the DNA Damage Response in Purkinje Cells Using Cerebellar Organotypic Cultures08:41

Visualizing the DNA Damage Response in Purkinje Cells Using Cerebellar Organotypic Cultures

Published on: December 27, 2024

Related Concept Videos

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...
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...