How does DNA damage activate ATM?

DNA damage caused by ionising radiation (double-strand DNA breaks) somehow activates the kinase activity of ATM (see below). ATR kinase activity is activated primarily in response to a different set of DNA lesions, including those caused by UV light, and in response to stalled replication forks.

Is ATM involved in Nhej?

However, under ATM inhibition, because ATM is essential for the initiation of resection, NHEJ can repair the DSBs, i.e., DSBs are repaired by NHEJ in ATM and KAP-1 double depleted cells.

Which two pathways can ATM activate?

Cellular responses to DNA damage are coordinated primarily by two distinct kinase signaling cascades, the ATM-Chk2 and ATR-Chk1 pathways, which are activated by DNA double-strand breaks (DSBs) and single-stranded DNA respectively.

What is ATM and ATR in cell cycle?

Ataxia-Telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) are members of the phosphatidyl inositol 3-kinase-like family of serine/threonine protein kinases (PIKKs), and play important roles in the cellular response to DNA damage.

What is ATM loss?

ATM Loss is a predictive biomarker for use of olaparib in patients. Of the therapies with ATM Loss as a predictive biomarker, 1 is FDA-approved and 1 has NCCN guidelines in at least one clinical setting. Prostate carcinoma has the most therapies targeted against ATM Loss or its related pathways [5].

What is ATM pathway?

The ataxia-telangiectasia mutated (ATM) kinase plays a critical role in the DNA damage response (DDR) as a sensor and signal transducer. Upon detection of DNA damage, inactive dimers of ATM are phosphorylated to form active monomers, which go on to phosphorylate numerous other signaling proteins.

What is Chk1 gene?

Checkpoint kinase 1, commonly referred to as Chk1, is a serine/threonine-specific protein kinase that, in humans, is encoded by the CHEK1 gene. Chk1 coordinates the DNA damage response (DDR) and cell cycle checkpoint response.

What is ATR in DNA?

ATR is a serine/threonine-specific protein kinase that is involved in sensing DNA damage and activating the DNA damage checkpoint, leading to cell cycle arrest in eukaryotes. ATR is activated in response to persistent single-stranded DNA, which is a common intermediate formed during DNA damage detection and repair.

What is ATM gene mutation?

Researchers have identified several hundred mutations in the ATM gene that cause ataxia-telangiectasia. People with this disorder have mutations in both copies of the ATM gene in each cell. Most of these mutations disrupt protein production, resulting in an abnormally small, nonfunctional version of the ATM protein.

What happens when ATM is mutated?

If You Carry an ATM Mutation, What Cancers Are You at Risk For? People who inherit two abnormal copies of ATM, one from each of their parents, develop ataxia-telangiectasia (A-T) — a rare disease that causes neurological problems and a less-productive immune system.