Related Experiment Video

Updated: Mar 27, 2026

Author Spotlight: Deciphering the Role of ATM in Ataxia-Telangiectasia and the Associated Cerebellar Degeneration

Author Spotlight: Deciphering the Role of ATM in Ataxia-Telangiectasia and the Associated Cerebellar Degeneration

Published on: December 27, 2024

The ATM- and ATR-related SCD domain is over-represented in proteins involved in nervous system development

Lukas Cara¹, Medina Baitemirova¹, Jack Follis²

¹Department of Biology, University of St. Thomas, Houston, TX, USA.

Scientific Reports

|January 9, 2016

Abstract:

ATM and ATR are cellular kinases with a well-characterized role in the DNA-damage response. Although the complete set of ATM/ATR targets is unknown, they often contain clusters of S/TQ motifs that constitute an SCD domain. In this study, we identified putative ATM/ATR targets that have a conserved SCD domain across vertebrates. Using this approach, we have identified novel putative ATM/ATR targets in pathways known to be under direct control of these kinases. Our analysis has also unveiled significant enrichment of SCD-containing proteins in cellular pathways, such as vesicle trafficking and actin cytoskeleton, where a regulating role for ATM/ATR is either unknown or poorly understood, hinting at a much broader and overarching role for these kinases in the cell. Of particular note is the overrepresentation of conserved SCD-containing proteins involved in pathways related to neural development. This finding suggests that ATM/ATR could be directly involved in controlling this process, which may be linked to the adverse neurological effects observed in patients with mutations in ATM.

Insights

This study identifies new targets for ATM and ATR kinases by analyzing conserved domains. These findings reveal ATM/ATR

Area of Science:

Molecular Biology
Cell Biology
Genetics

Background:

ATM and ATR are key kinases in DNA damage response.
Their complete target repertoire and functions beyond DNA repair are not fully understood.
ATM/ATR targets often possess Serine/Threonine-Tyrosine (S/TQ) motif clusters forming Substrate Consensus Domains (SCDs).

Purpose of the Study:

To identify novel ATM/ATR kinase targets using conserved SCD domains across vertebrates.
To explore the broader regulatory roles of ATM/ATR in cellular pathways.
To investigate the potential involvement of ATM/ATR in neural development.

Main Methods:

Bioinformatic analysis to identify conserved SCD domains in vertebrate proteins.
Comparative genomics to pinpoint putative ATM/ATR targets.
Pathway enrichment analysis to determine cellular functions of identified targets.

Main Results:

Identified novel putative ATM/ATR targets with conserved SCD domains.
Discovered significant enrichment of SCD-containing proteins in vesicle trafficking and actin cytoskeleton pathways.
Found overrepresentation of conserved SCD-containing proteins in neural development pathways.

Conclusions:

ATM/ATR kinases may regulate pathways beyond DNA damage response, including vesicle trafficking and actin cytoskeleton dynamics.
ATM/ATR kinases are potentially involved in neural development, offering insights into neurological disorders linked to ATM mutations.
The conserved SCD domain serves as a reliable marker for identifying ATM/ATR targets.

Read full analysis

More Related Videos

Retrograde Tracing of Drosophila Embryonic Motor Neurons Using Lipophilic Fluorescent Dyes

Retrograde Tracing of Drosophila Embryonic Motor Neurons Using Lipophilic Fluorescent Dyes

Published on: January 12, 2020

Cerebellar Regional Dissection for Molecular Analysis

Cerebellar Regional Dissection for Molecular Analysis

Published on: December 5, 2020

Related Concept Videos

Cadherins in Tissue Organization

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...

Autonomic Nervous System: Overview

Autonomic Nervous System: Overview

The human nervous system is divided into two main parts: the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS is composed of the brain and spinal cord, while the PNS contains nerve cells, clusters of nerve cells, and the sensory receptors that are outside the CNS. The PNS has two types of nerve cells: sensory (afferent) and motor (efferent). Sensory cells send signals to the CNS from receptors, and motor cells carry signals from the CNS to organs, muscles, and...

Autonomic Nervous System

Autonomic Nervous System

The autonomic nervous system (ANS) is a critical component of the peripheral nervous system, primarily responsible for regulating involuntary bodily functions and maintaining homeostasis. It functions in tandem with the central nervous system (CNS) to seamlessly coordinate various physiological processes without the need for conscious control.
The ANS comprises two main divisions: the sympathetic and parasympathetic divisions. These divisions function antagonistically to maintain a dynamic...

Assembly of Signaling Complexes

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...

Articles linked to this work by shared authors, journal, and citation graph.

Differentiation of Active Corneal Infections from Healed Scars Using Deep Learning.

Ophthalmology·2021

Ku DNA End-Binding Activity Promotes Repair Fidelity and Influences End-Processing During Nonhomologous End-Joining in Saccharomyces cerevisiae.

Genetics·2018

Using a PyMOL activity to reinforce the connection between genotype and phenotype in an undergraduate genetics laboratory.

PloS one·2014

An interictal EEG spectral metric for temporal lobe epilepsy lateralization.

Epilepsy research·2014

SCDFinder, a web-based tool for the identification of putative novel ATM and ATR targets.

Bioinformatics (Oxford, England)·2014

TRF2 interaction with Ku heterotetramerization interface gives insight into c-NHEJ prevention at human telomeres.

Cell reports·2013

See all related articles