ATM

ATM serine/threonine kinase

Gene Information

Gene Symbol
ATM
Aliases
TEL1, TELO1, ATA, ATDC, ATC, ATD
HGNC ID
HGNC:795
NCBI Gene ID
472
Ensembl Gene ID
ENSG00000149311
Gene Type
protein coding

Genomic Location

Chromosome
11
Assembly
GRCh38
Start Position
108,222,804
End Position
108,369,102
Number of Exons
63
Gene Length
146,299 bp

Overview

ATM is involved diverse aspects of cellular physiology including DNA repair and cell cycle control. It appears to activate DNA repair pathways in response to DNA damage. Mutations in human ATM cause ataxia telangiectasia, an early-onset disease some argue is characterized by signs of premature ageing. Patients display cerebellar atrophy and neurodegeneration. In mouse and worm models that are ATM deficient replenishing intracellular NAD+ reduces the severity of neuropathy, normalizes neuromuscular function, delays memory loss, and extends lifespan. In mice, mutations in ATM in late-generation TERC mutants with short telomeres results in signs of premature ageing starting at about 6 months of age. In mouse and human cells ATM is required for the recruitment of telomerase and inhibition of ATM leads to shortening of telomeres. However, it has also been shown that inhibiting ATM attenuates senescence. Inhibiting ATM induces the functional recovery of the lysosome/autophagy system and accelerates the removal of dysfunctional mitochondria. Overall, it is possible ATM plays a role in human ageing and may link two major theories on ageing: DNA damage accumulation and mitochondrial dysfunction.

Research Papers

20 papers in databaseSearch for More Papers
#1
Score:
90%

Tandem Deubiquitination and Acetylation of SPRTN Promotes DNA-Protein Crosslink Repair and Protects against Aging.

Mol Cell
2020
PMID: 32649882

Modification Effects

Deubiquitination of SPRTN by VCPIP1; subsequent acetylation promotes chromatin relocalization and DNA-protein crosslink repair

Longevity Association

Premature aging in Vcpip1 knockout mice; mechanism: genomic instability due to impaired DNA-protein crosslink repair

#2
Score:
90%

Atm reactivation reverses ataxia telangiectasia phenotypes in vivo.

Cell Death Dis
2018
PMID: 29472706

Modification Effects

ATM kinase reactivation; restored DNA double-strand break repair function

Longevity Association

Doubled lifespan in Atm-deficient mice; mechanism: restored DNA damage signaling and repair

#3
Score:
90%

Atrx deficiency induces telomere dysfunction, endocrine defects, and reduced life span.

J Clin Invest
2013
PMID: 23563309

Modification Effects

ATRX deficiency; telomere dysfunction, replicative damage, and increased sensitivity to replication stress

Longevity Association

Shortened life span in mice; mechanism: increased DNA damage, tissue attrition, and endocrine defects

#4
Score:
80%

Mitochondria are required for pro-ageing features of the senescent phenotype.

EMBO J
2016
PMID: 26848154

Longevity Association

Reduced senescence in ageing mouse liver; mechanism: inhibition of mTORC1 or deletion of PGC-1beta, reducing mitochondrial content and subsequent ROS-mediated DDR activation

#5
Score:
80%

LARP7 ameliorates cellular senescence and aging by allosterically enhancing SIRT1 deacetylase activity.

Cell Rep
2021
PMID: 34818543

Modification Effects

LARP7 enhances SIRT1 deacetylase activity; deletion of LARP7 dampens SIRT1 activity, increases p53 and NF-kappaB acetylation

Longevity Association

Prevention of LARP7 downregulation alleviates senescence and atherogenesis; rodent model shows premature aging upon LARP7 deletion; mechanism: reduced DNA damage response and oxidative stress

#6
Score:
80%

Rare genetic associations with human lifespan in UK Biobank are enriched for oncogenic genes.

Nat Commun
2025
PMID: 40021682

Modification Effects

Loss-of-function variants in TET2, ATM, BRCA2, CKMT1B, BRCA1, ASXL1; pathogenic missense variants in DNMT3A, SF3B1, TET2, PTEN, SOX21, TP53, SRSF2, RLIM; altered oncogenic pathways

Longevity Association

Reduced lifespan associated with cancer-related genes; population study in UK Biobank (European ancestry); mechanism: oncogenic pathways and clonal hematopoiesis

#7
Score:
80%

Topological stress triggers persistent DNA lesions in ribosomal DNA with ensuing formation of PML-nucleolar compartment.

Elife
2024
PMID: 39388244

Longevity Association

Cells with persistent PML-nucleolar associations undergo senescence; implications for tumorigenesis and aging

#8
Score:
80%

Damage-Free Shortening of Telomeres Is a Potential Strategy Supporting Blind Mole-Rat Longevity.

Genes (Basel)
2023
PMID: 37107603

Modification Effects

Telomere shortening; lower telomerase activity; decline in shelterin protein mRNA expression

Longevity Association

Contribution to longevity and healthy aging in blind mole-rats (Spalax); mechanism: effective telomere maintenance, prevention of early cellular senescence and persistent DNA damage response

#9
Score:
80%

Unique ligand and kinase-independent roles of the insulin receptor in regulation of cell cycle, senescence and apoptosis.

Nat Commun
2023
PMID: 36599833

Modification Effects

K1030R mutation or beta-subunit deletion; altered phosphorylation of proteins involved in cell cycle, senescence, and apoptosis regulation

#10
Score:
80%

Chk2 deletion rescues bone loss and cellular senescence induced by Bmi1 deficiency via regulation of Cyp1a1.

J Orthop Translat
2025
PMID: 40698069

Modification Effects

Chk2 deletion; reduced oxidative stress and senescence through downregulation of Cyp1a1

Longevity Association

Rescue of bone loss and cellular senescence in Bmi1-deficient mice; improved bone mineral density and trabecular bone volume; mechanism: reduced oxidative stress via Cyp1a1 downregulation

#11
Score:
80%

The burden of rare protein-truncating genetic variants on human lifespan.

Nat Aging
2022
PMID: 37117740

Modification Effects

Protein-truncating variants (PTVs) in BRCA1, BRCA2, ATM, and TET2; loss of function

Longevity Association

Association with human lifespan, particularly through cancer and clonal hematopoiesis mechanisms; modest overlap with common variant-based GWASs

#12
Score:
80%

Alternative telomere maintenance mechanism in Alligator sinensis provides insights into aging evolution.

iScience
2023
PMID: 36636341

Modification Effects

Repressed ATM kinase activity; altered expression of ALT-related genes

Longevity Association

Negligible mortality in adult Alligator sinensis; mechanism: alternative telomere maintenance via ALT, no significant telomere shortening

#13
Score:
80%

Inhibition of ATM kinase rescues planarian regeneration after lethal radiation.

EMBO Rep
2023
PMID: 36943023

Modification Effects

ATM kinase inhibition; circumvention of apoptosis, enhanced DNA repair via homologous recombination

Longevity Association

Long-term survival and regeneration in planarian flatworms after lethal radiation; mechanism: inhibition of ATM-dependent apoptosis

#14
Score:
80%

Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length.

Am J Hum Genet
2020
PMID: 32109421

Longevity Association

Genetically shorter telomere length associated with increased risk of hypothyroidism, coronary artery disease, and decreased risk of thyroid cancer, lymphoma; human study with >350,000 UK Biobank participants

#15
Score:
80%

Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans.

Sci Transl Med
2013
PMID: 23408054

Modification Effects

Impaired ATM-mediated DNA double-strand break repair; declined expression of BRCA1, MRE11, Rad51, and ATM genes

Longevity Association

Impaired reproductive capacity, reduced primordial follicle counts, and increased DNA double-strand breaks in Brca1-deficient mice and humans; mechanism: impaired DNA repair efficiency

#16
Score:
80%

Transient induction of telomerase expression mediates senescence and reduces tumorigenesis in primary fibroblasts.

Proc Natl Acad Sci U S A
2019
PMID: 31481614

Modification Effects

TERT expression up-regulation; protective role against senescence and malignant transformation

Longevity Association

Delayed senescence and reduced tumorigenesis in primary fibroblasts; mechanism: telomerase-mediated telomere elongation

#17
Score:
80%

Nbn and atm cooperate in a tissue and developmental stage-specific manner to prevent double strand breaks and apoptosis in developing brain and eye.

PLoS One
2013
PMID: 23935957

Modification Effects

Mutations in NBN or ATM; increased DNA double strand breaks and apoptosis

Longevity Association

Reduced lifespan in Nbn-deficient mice with Atm inactivation in central nervous system; mechanism: increased DSBs and apoptosis during neural development

#18
Score:
80%

Ablation of XP-V gene causes adipose tissue senescence and metabolic abnormalities.

Proc Natl Acad Sci U S A
2015
PMID: 26240351

Modification Effects

XP-V gene ablation; increased DNA damage and senescence markers (p53, p16, p21, gammaH2AX, PARP-1) in adipose tissue

Longevity Association

Adipose tissue senescence and metabolic abnormalities (obesity, insulin resistance) in mice; mechanism: elevated DNA damage and oxidative stress

#19
Score:
80%

The cGAS-STING, p38 MAPK, and p53 pathways link genome instability to accelerated cellular senescence in ATM-deficient murine lung fibroblasts.

Proc Natl Acad Sci U S A
2025
PMID: 39772747

Modification Effects

ATM deficiency; collaborative action of cGAS-STING, p38 MAPK, and p53 pathways; induction of interferon-alpha1 and downstream interferon-stimulated genes

Longevity Association

Accelerated cellular senescence in ATM-deficient murine lung fibroblasts; contributes to premature aging and interstitial lung disease; mechanism: persistent DNA damage and genomic instability

#20
Score:
80%

Growing old, yet staying young: The role of telomeres in bats' exceptional longevity.

Sci Adv
2018
PMID: 29441358

Longevity Association

Exceptional longevity in Myotis bats; mechanism: telomere maintenance through differential expression of 21 genes, including ATM and SETX for DNA repair

Return to Knowledge Base