Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Endogenous topoisomerase II-mediated DNA breaks drive thymic cancer predisposition linked to ATM deficiency

ABSTRACT: Copy-number variation by Comparative Genomic Hybridization (CGH) on thymocytes and Kidney (control) of Tdp2+/+Atm-/- and Tdp2-/-Atm-/- mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE134054 | GEO | 2019/12/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Endogenous topoisomerase II-mediated DNA breaks drive thymic cancer predisposition linked to ATM deficiency

Project description:The ATM kinase is a master regulator of the DNA damage response to double-strand breaks (DSBs) and a well-established tumour suppressor. Loss-of-function mutations in the gene are not only frequently found in many types of cancer, but constitute the underlying cause of the neurodegenerative and cancer-prone genetic syndrome Ataxia-Telangiectasia (A-T). A-T patients are particularly predisposed to develop lymphoid cancers, which are thought to arise from inefficient signalling and inaccurate repair of RAG-induced DSBs during V(D)J recombination, and which the Atm-/- mouse models recapitulate in the form of very aggressive T-cell malignancies. Here, we unexpectedly find that specifically disturbing the repair of DSBs produced by DNA topoisomerase II (TOP2) by genetically removing the highly specialised repair enzyme TDP2, strongly increases the incidence of thymic tumours in Atm-/- mice, but without changing their molecular characteristics or underlying genomic rearrangements, including a significant association with Tcr loci. Furthermore, we find that TOP2 strongly colocalizes with RAG, both in a genome-wide scale and specifically at sites undergoing V(D)J recombination, in a manner that is consistent with its involvement in solving topological problems associated to 3D genome organization, and which results in an increased chromosomal fragility of these regions. Thus, our findings demonstrate a strong causal relationship between accidental TOP2-induced DSBs and cancer development, putting forward these lesions as major drivers of the genome rearrangements that are characteristic of ATM-deficient lymphoid malignancies, and opening the door for their involvement in other conditions and cancer types.

2019-12-23 | GSE133954 | GEO

Endogenous topoisomerase II-mediated DNA breaks drive thymic cancer predisposition linked to ATM deficiency.

Project description: Not available

| S-EPMC7021672 | biostudies-literature

Endogenous topoisomerase II-mediated DNA breaks drive thymic cancer predisposition linked to ATM deficiency

Project description:Endogenous topoisomerase II-mediated DNA breaks drive thymic cancer predisposition linked to ATM deficiency

| PRJNA553571 | ENA

Endogenous topoisomerase II-mediated DNA breaks drive thymic cancer predisposition linked to ATM deficiency

Project description:Endogenous topoisomerase II-mediated DNA breaks drive thymic cancer predisposition linked to ATM deficiency

| PRJNA553208 | ENA

Murine Atm deficient thymocytes vs. murine wildtype thymocytes

Project description:genomic profiling of murine thymocytes of Atm deficient mice with and without T-cell lymphoma Keywords: genetic modification

2008-07-15 | GSE10844 | GEO

Expression profiling of Atm deficient murine thymic lymphoma

Project description:To find genes deregulated in the pathogenisis of T-cells in Atm deficient mice, we performed expression profiling of Atm deficient thymic lymphomas, wildtype thymi and Atm deficient thymi without macroscopic enlargement, representing an intermediate stage in the process of tumorigenisis. Keywords: genetic modification, disease state analysis

2008-07-15 | GSE10807 | GEO

Non redundant functions of ATM and DNAPKcs in response to clean DNA Double Strand Breaks.

Project description:DNA Double Strand Breaks (DSBs) are harmful lesions that require rapid detection and repair in order to avoid toxic genomic rearrangements. DSBs elicit the so called DNA Damage Response (DDR), largely relying on ataxia telangiectasia mutated (ATM) and DNA Protein Kinase (DNAPK), two members of the PI3K-like kinase family, whose respective functions during the sequential steps of the DDR remains controversial. Using the DIvA cell line, expressing the AsiSI restriction enzyme, we have investigated the role of ATM and DNAPK in several aspects of the DDR upon induction of multiple clean DSBs throughout the human genome. High resolution mapping revealed that they are activated and spread in cis on a confined region surrounding all DSBs, independently of the pathway used for repair. However, a thorough analysis of repair kinetics, H2AX domain establishment and H2AX foci structure and dynamics revealed non overlapping functions for the two kinases once recruited at DSBs. Our results suggest that ATM is not solely acting on chromatin marks but also on chromatin organisation in order to ensure repair accuracy and survival.

2015-09-30 | E-MTAB-2992 | biostudies-arrayexpress

Panicum virgatum strain:ATM | cultivar:ATM

Project description:Panicum virgatum ATM Resequencing genome sequencing

| PRJNA332580 | ENA

MiRNAs expression data from Atm++ and Atm-- mouse embryonic fibroblasts after DNA damage at various time point

Project description:Atm++ and Atm-- mouse embryonic fibroblasts were treated with DNA damaging agent neocarzinostatin (NCS), and cells were harvested at indicated time points for the microarray analyses of whole-genome miRNAs. To examine how miRNAs are regulated in the DNA damage response, we assessed the genome-wide mature miRNA expression in Atm++ and Atm-- littermate mouse embryonic fibroblasts (MEFs).

2010-12-20 | E-TABM-1092 | biostudies-arrayexpress

MiRNAs expression data from Atm+/+ and Atm-/- mouse embryonic fibroblasts after DNA damage at various time point

Project description:Atm+/+ and Atm-/- mouse embryonic fibroblasts were treated with DNA damaging agent neocarzinostatin (NCS), and cells were harvested at indicated time points for the microarray analyses of whole-genome miRNAs. To examine how miRNAs are regulated in the DNA damage response, we assessed the genome-wide mature miRNA expression in Atm+/+ and Atm-/- littermate mouse embryonic fibroblasts (MEFs).

2010-12-09 | E-GEOD-25916 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data