ATM Gene

ATM serine/threonine kinase, along with the closely related ATR kinase, is thought to control cell cycle checkpoint signaling pathways that are required for the cell's response to DNA damage and for genome stability (Negrini S et al. 2010).

Specifically, ATM serine/threonine protein kinase acts as a sensor for DNA damage by activating checkpoint signaling. This cascade is activated, for example, during double-strand breaks (DSBs), apoptosis, and genotoxic stress (Shiloh Y et al. 2013) such as ionizing UV radiation. Protein kinase recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX upon double strand breaks (DSBs), regulating DNA - damage response mechanism.

The enzyme also plays a role in allelic exclusion of pre-B cells, a process that results in the expression of a single allele of the immunoglobulin heavy chain to enhance clonality and monospecific recognition by the B cell antigen receptor (BCR) expressed on individual B lymphocytes. It is also involved in signal transduction and cell cycle control. ATM-serine/threonine protein kinase may function as a tumor suppressor. ATM-serine/threonine protein kinase could possibly play a role in vesicle and/or protein transport. Furthermore, in the development of T cells, gonads and neurological functions. Plays a role in replication-dependent histone mRNA degradation. Binds DNA ends.

Diseases associated with ATM include:

• the autosomal recessive ataxia-telangiectatica
• and
• the mantle cell lymphoma.

Furthermore, individuals with ataxia telangiectasia (Louis-Bar syndrome) have a cluster of T-cell prolymphocytic leukemia (with an earlier median age between 25-30 years - Suarez F et al. 2015).

1. Negrini S et al (2010) Genomic instability--an evolving hallmark of cancer. Nat Rev Mol Cell Biol 11:220-228.
2. Shiloh Y et al. (2013) The ATM protein kinase: regulating the cellular response to genotoxic stress, and more. Nat Rev Mol Cell Biol 14:197-210.
3. Suarez F et al. (2015) Incidence, presentation, and prognosis of malignancies in ataxia-telangiectasia: a report from the French national registry of primary immune deficiencies. J Clin Oncol 33:202-208.
4. Yajima H et al. (2009) DNA double-strand break formation upon UV-induced replication stress activates ATM and DNA-PKcs kinases. J Mol Biol 385: 800-810.