Role of ATM in cellular responses

Role of ATM in cellular responses. ATM kinase activity increases immediately after exposure to ionizing radiation (IR). ATM mediates the early stages of the rapid induction of several signaling pathways, which include regulation of the cell-cycle checkpoint controls, activation of the DNA-DSB (double-strand break) repair pathway, activation of stress responses, and maintenance of telomeres. ‘P’ with black solid arrows indicates reported phosphorylation events; dashed arrows represent possible signaling steps and do not imply direct interaction between proteins; ‘C’ indicates sequestering in cytoplasm; ‘R’ indicates repair complexes; and ‘T’ indicates a role for the protein in telomere metabolism. ATM influences telomere function through direct interaction with TRF1. In addition, c-Abl phosphorylates hTERT and negatively regulates telomerase activity. The other downstream effector of ATM in telomere metabolism is 14-3-3σ. Abbreviations: AP-1: Apetala1 transcription factor; BRCA1: breast cancer susceptibility gene product 1; cAbl: Abelson protein tyrosine kinase; Cdc2: cyclinB; CDC25: cell division cycle 25; Cdk2: cyclin-dependent kinase; CHK: checkpoint kinase; CyA, CyB, CyE: cyclinA, cyclin B, cyclin E; FANCD2: Fanconi anaemia protein; hSSB1: human single strand DNA binding protein; hTERT: human catalytic unit of telomerase; JNK: Jun N-terminal protein kinase; KAP1: co-repressor of KRAB associated proein; MDC1: mediator of damage checkpoint 1; MRE11: meiotic recombination 11 gene product; MDM2: mouse double minute 2 (p53-binding protein); NBS1: Nijmegen breakage syndrome 1 protein (p95); RAD50: a radiation-damage-repair-associated protein; SMC1: structural maintenance of chromosome 1; TRF1: telomere-repeat-finding factor 1; MOF and Tip60 are members of the MYST family and have histone acetyltranferase activity, which has been implicated in ATM function.

Publication

Telomeres, histone code, and DNA damage response. () S. Misri, et al. Cytogenet Genome Res. ;122(3-4):297-307. Figure: F1. All organisms Homo sapiens Mus musculus Drosophila melanogaster Schizosaccharomyces pombe Caenorhabditis elegans

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