Cancer Susceptibility Pathway

Preferred Label : Cancer Susceptibility Pathway;

NCIt related terms : Role of BRCA1, BRCA2 and ATR in Cancer Susceptibility;

Alternative definition : BIOCARTA: BRCA1 and BRCA2 were identified genetically as breast cancer susceptibility genes when a single copy of the gene is mutated and are involved in the cellular response to DNA damage, including blocking cell cycle progression and inducing DNA repair to preserve the integrity of the genome during cell division. BRCA1 and BRCA2 induce double-stranded repair of breaks using homologous recombination, in part through activation of RAD51. BRCA1 acts as a ubiquitin ligase targeting the protein FancD2 that activates checkpoint control, integrating the ATM response to ionizing radiation and the FA response to cross-linking agents like mitomycin C. Mutation of one of the several components of the FA complex involved in maintaining integrity of the genome leads to the condition Fanconi anemia. One member of the FA complex was recently identified as BRCA2, which leads to Fanconi anemia when both copies of the gene are mutated. Another related factor involved in the response of cells to DNA damage is the kinase ATM. ATM is mutated in patients with AT, a condition with many similar traits to Fanconi anemia. Like ATM, ATR serves as a checkpoint kinase that halts cell cycle progression and induces DNA repair when DNA is damaged. Loss of ATR results in a loss of checkpoint control in response to DNA damage, leading to cell death. Deletion of the ATR gene in mice is embryonic lethal. ATRIP is a protein that interacts with ATR and is a substrate for its kinase activity. ATRIP is required for ATR function, and removal of ATRIP also leads to a loss of checkpoint control of the cell cycle. ATR and ATM kinase targets include repair enzymes like Rad51, and the checkpoint kinases Chk1 and Chk2, as well as BRCA1 and BRCA2. The close relationship of the genes involved in breast cancer and Fanconi anemia has helped illuminate this signaling system, and may help lead to improved understanding and treatment of these conditions. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_atrbrcaPathway;

Details

Origin ID

C38997;

UMLS CUI

C1516233;

Semantic type(s)
- Genetic Function [UMLS semantic type]
has_gene_product_element
- Breast Cancer Type 1 Susceptibility Protein [NCIt concept]
- Breast Cancer Type 2 Susceptibility Protein [NCIt concept]
- Cell Cycle Checkpoint Control Protein RAD9A [NCIt concept]
- Cellular Tumor Antigen p53 [NCIt concept]
- DNA Repair Protein RAD50 [NCIt concept]
- DNA Repair Protein RAD51 Homolog 1 [NCIt concept]
- Double-Strand Break Repair Protein MRE11 [NCIt concept]
- Fanconi Anemia Group A Protein [NCIt concept]
- Fanconi Anemia Group B Protein [NCIt concept]
- Fanconi Anemia Group C Protein [NCIt concept]
- Fanconi Anemia Group D2 Protein [NCIt concept]
- Fanconi Anemia Group E Protein [NCIt concept]
- Fanconi Anemia Group F Protein [NCIt concept]
- Fanconi Anemia Group G Protein [NCIt concept]
- Nibrin [NCIt concept]
- Serine-Protein Kinase ATM [NCIt concept]
- Serine/Threonine-Protein Kinase ATR [NCIt concept]
- Serine/Threonine-Protein Kinase Chk1 [NCIt concept]
- Serine/Threonine-Protein Kinase Chk2 [NCIt concept]
- Three Prime Repair Exonuclease 1 [NCIt concept]
pathway_has_gene_element
- ATM wt Allele [NCIt concept]
- ATR wt Allele [NCIt concept]
- BRCA1 wt Allele [NCIt concept]
- BRCA2 wt Allele [NCIt concept]
- CHEK1 wt Allele [NCIt concept]
- CHEK2 wt Allele [NCIt concept]
- FANCA wt Allele [NCIt concept]
- FANCC wt Allele [NCIt concept]
- FANCD2 wt Allele [NCIt concept]
- FANCE wt Allele [NCIt concept]
- FANCF wt Allele [NCIt concept]
- FANCG wt Allele [NCIt concept]
- MRE11 wt Allele [NCIt concept]
- NBN wt Allele [NCIt concept]
- RAD50 wt Allele [NCIt concept]
- RAD51 wt Allele [NCIt concept]
- RAD9A wt Allele [NCIt concept]
- TP53 wt Allele [NCIt concept]
- TREX1 wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

You can consult :

recommendations
documents concerning education
documents for patients