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Published on: January 31, 2018
ATM-dependent pathways of chromatin remodelling and oxidative DNA damage responses
N Daniel Berger1, Fintan K T Stanley1, Shaun Moore1
1Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Departments of Biochemistry & Molecular Biology and Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
Abstract:
Ataxia-telangiectasia mutated (ATM) is a serine/threonine protein kinase with a master regulatory function in the DNA damage response. In this role, ATM commands a complex biochemical network that signals the presence of oxidative DNA damage, including the dangerous DNA double-strand break, and facilitates subsequent repair. Here, we review the current state of knowledge regarding ATM-dependent chromatin remodelling and epigenomic alterations that are required to maintain genomic integrity in the presence of DNA double-strand breaks and/or oxidative stress. We will focus particularly on the roles of ATM in adjusting nucleosome spacing at sites of unresolved DNA double-strand breaks within complex chromatin environments, and the impact of ATM on preserving the health of cells within the mammalian central nervous system.This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'.
Insights
Ataxia-telangiectasia mutated (ATM) kinase regulates DNA damage response, orchestrating chromatin remodelling and epigenomic alterations to maintain genomic integrity. This review focuses on ATM
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Ataxia-telangiectasia mutated (ATM) is a key serine/threonine protein kinase.
- ATM plays a crucial role in the DNA damage response, particularly for oxidative DNA damage and double-strand breaks.
Purpose of the Study:
- To review ATM-dependent chromatin remodelling and epigenomic alterations in maintaining genomic integrity.
- To highlight ATM's role in nucleosome spacing at DNA double-strand break sites.
- To discuss ATM's impact on mammalian central nervous system cell health.
Main Methods:
- Literature review of ATM's function in DNA repair.
- Analysis of ATM's role in chromatin structure and epigenomic modifications.
- Focus on ATM's impact on DNA double-strand break repair and cellular health.
Main Results:
- ATM signaling is essential for coordinating DNA damage response pathways.
- ATM influences chromatin structure, including nucleosome spacing, at DNA damage sites.
- ATM activity is critical for preserving genomic integrity and neuronal health.
Conclusions:
- ATM-dependent chromatin and epigenomic changes are vital for genomic stability under stress.
- Understanding ATM's mechanisms offers insights into DNA repair and neuroprotection.
- This review synthesizes current knowledge on ATM's multifaceted role in DNA repair and cellular maintenance.
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