ATR is activated in response to single strand breaks, and works with ATM to ensure genome integrity.

ATR works with a partner protein called ATRIP to recognize single-stranded DNA coated with RPA.

Instead, ATR activation is heavily dependent on the existence of all the proteins previously described, that colocalize around the site of DNA damage.

An experiment where RAD9, ATRIP, and TOPBP1 were overexpressed proved that these proteins alone were enough to activate ATR in the absence of ssDNA, showing their importance in triggering this pathway.

[11] Once ATR is activated, it phosphorylates Chk1, initiating a signal transduction cascade that culminates in cell cycle arrest.

[11] This claspin intermediate needs to be phosphorylated at two sites in order to do this job, something that can be carried out by ATR but is most likely under the control of some other kinase.

[11] ATR is related to a second checkpoint-activating kinase, ATM, which is activated by double strand breaks in DNA or chromatin disruption.

The total knockout of ATR is responsible for early death of mouse embryos, showing that it is a protein with essential life functions.

In this setting, ATR is essential to preventing fork collapse, which would lead to extensive double strand breakage across the genome.

[19] One study by Flynn et al. found that ATR inhibitors work especially well in cancer cells which rely on the alternative lengthening of telomeres (ALT) pathway.

[23] Furthermore, there are dramatic reductions with age in tissue-specific stem and progenitor cells, and exhaustion of tissue renewal and homeostatic capacity.

Sequencing revealed that this ATRIP mutation occurred most likely due to missplicing which led to fragments of the gene without exon 2.

Both of these mutations resulted in lower levels of ATR and ATRIP than in wild-type cells, leading to insufficient DNA damage response and the severe form of Seckel Syndrome noted above.

[25] Somatic cells of mice deficient in ATR have a decreased frequency of homologous recombination and an increased level of chromosomal damage.

[27] During mitosis in Drosophila DNA damages caused by exogenous agents are repaired by a homologous recombination process that depends on mei-41(ATR).

Mutants defective in mei-41(ATR) have increased sensitivity to killing by exposure to the DNA damaging agents UV ,[28] and methyl methanesulfonate.