ATM is activated by mechanisms that sense double stranded DNA breaks. ATM transmits signals to arrest the cell cycle after DNA damage. It acts through p53 in the G1/S checkpoint.

At the G2/M checkpoint, ATM acts both through p53-dependent mechanisms and through the inactivation of CDC25 phosphatase, which disrupts the cyclin B-CDK1 complex. Component of a network of genes that include BRCA1 and BRCA2, which link DNA damage with cell-cycle arrest and apoptosis.

Pathology

 mutations in ataxia-telangiectasia
 mutation/deletion in rhabdomyosarcoma (#12673126#)

Free references

 Yang J, Xu ZP, Huang Y, Hamrick HE, Duerksen-Hughes PJ, Yu YN. ATM and ATR: sensing DNA damage. World J Gastroenterol. 2004 Jan 15;10(2):155-60. PMID: #14716813#

 Huber A, Bai P, de Murcia JM, de Murcia G. PARP-1, PARP-2 and ATM in the DNA damage response: functional synergy in mouse development. DNA Repair (Amst). 2004 Aug-Sep;3(8-9):1103-8. PMID: #15279798#

 Shiloh Y, Andegeko Y, Tsarfaty I. In search of drug treatment for genetic defects in the DNA damage response: the example of ataxia-telangiectasia. Semin Cancer Biol. 2004 Aug;14(4):295-305. PMID: #15219622#

 Lavin MF, Birrell G, Chen P, Kozlov S, Scott S, Gueven N. ATM signaling and genomic stability in response to DNA damage. Mutat Res. 2005 Jan 6;569(1-2):123-32. PMID: #15603757#

 Lavin MF, Scott S, Gueven N, Kozlov S, Peng C, Chen P. Functional consequences of sequence alterations in the ATM gene. DNA Repair (Amst). 2004 Aug-Sep;3(8-9):1197-205. PMID: #15279808#

 Chun HH, Gatti RA. Ataxia-telangiectasia, an evolving phenotype. DNA Repair (Amst). 2004 Aug-Sep;3(8-9):1187-96. PMID: #15279807#

 Hammond EM, Giaccia AJ. The role of ATM and ATR in the cellular response to hypoxia and re-oxygenation. DNA Repair (Amst). 2004 Aug-Sep;3(8-9):1117-22. PMID: #15279800#

 Huber A, Bai P, de Murcia JM, de Murcia G. PARP-1, PARP-2 and ATM in the DNA damage response: functional synergy in mouse development. DNA Repair (Amst). 2004 Aug-Sep;3(8-9):1103-8. PMID: #15279798#

 Koundrioukoff S, Polo S, Almouzni G. Interplay between chromatin and cell cycle checkpoints in the context of ATR/ATM-dependent checkpoints. DNA Repair (Amst). 2004 Aug-Sep;3(8-9):969-78. PMID: #15279783#

 Abraham RT. The ATM-related kinase, hSMG-1, bridges genome and RNA surveillance pathways. DNA Repair (Amst). 2004 Aug-Sep;3(8-9):919-25. PMID: #15279777#

 Kurz EU, Lees-Miller SP. DNA damage-induced activation of ATM and ATM-dependent signaling pathways. DNA Repair (Amst). 2004 Aug-Sep;3(8-9):889-900. PMID: #15279774#

 McKinnon PJ. ATM and ataxia telangiectasia. EMBO Rep. 2004 Aug;5(8):772-6. PMID: #15289825#

 Gumy-Pause F, Wacker P, Sappino AP. ATM gene and lymphoid malignancies. Leukemia. 2004 Feb;18(2):238-42. PMID: #14628072#

 Shiloh Y. ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer. 2003 Mar;3(3):155-68. PMID: #12612651#

 Pandita TK. ATM function and telomere stability. Oncogene. 2002 Jan 21;21(4):611-8. PMID: #11850786#

 Kastan MB, Lim DS. The many substrates and functions of ATM. Nat Rev Mol Cell Biol. 2000 Dec;1(3):179-86. PMID: #11252893#

 Jeggo PA, Carr AM, Lehmann AR. Splitting the ATM: distinct repair and checkpoint defects in ataxia-telangiectasia. Trends Genet. 1998 Aug;14(8):312-6. PMID: #9724963#

 Rotman G, Shiloh Y. ATM: from gene to function. Hum Mol Genet. 1998;7(10):1555-63. PMID: #9735376#