Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor (PubMed:10597277, PubMed:10608806, PubMed:10859164, PubMed:11721054, PubMed:12791985, PubMed:12814551, PubMed:14657349, PubMed:14729973, PubMed:14742437, PubMed:15210935, PubMed:15496423, PubMed:16260606, PubMed:21144835, PubMed:21777809, PubMed:23273981, PubMed:25083873, PubMed:27723717, PubMed:27723720, PubMed:30139873, PubMed:33848395, PubMed:37788673, PubMed:37832547, PubMed:9427750, PubMed:9636169). Recognizes the substrate consensus sequence [ST]-Q (PubMed:10597277, PubMed:10608806, PubMed:10859164, PubMed:11721054, PubMed:12791985, PubMed:12814551, PubMed:14657349, PubMed:14729973, PubMed:14742437, PubMed:15210935, PubMed:15496423, PubMed:16260606, PubMed:21144835, PubMed:23273981, PubMed:27723717, PubMed:27723720, PubMed:33848395, PubMed:9427750, PubMed:9636169). Phosphorylates BRCA1, CHEK1, MCM2, RAD17, RBBP8, RPA2, SMC1 and p53/TP53, which collectively inhibit DNA replication and mitosis and promote DNA repair, recombination and apoptosis (PubMed:11114888, PubMed:11418864, PubMed:11865061, PubMed:21777809, PubMed:23273981, PubMed:25083873, PubMed:9925639).

Phosphorylates 'Ser-139' of histone variant H2AX at sites of DNA damage, thereby regulating DNA damage response mechanism (PubMed:11673449). Required for FANCD2 ubiquitination (PubMed:15314022). Critical for maintenance of fragile site stability and efficient regulation of centrosome duplication (PubMed:12526805).

Acts as a regulator of the S-G2 transition by restricting the activity of CDK1 during S-phase to prevent premature entry into G2 (PubMed:30139873). Acts as a regulator of the nuclear envelope integrity in response to DNA damage and stress (PubMed:25083873, PubMed:37788673, PubMed:37832547). Acts as a mechanical stress sensor at the nuclear envelope: relocalizes to the nuclear envelope in response to mechanical stress and mediates a checkpoint via phosphorylation of CHEK1 (PubMed:25083873).

Also promotes nuclear envelope rupture in response to DNA damage by mediating phosphorylation of LMNA at 'Ser-282', leading to lamin disassembly (PubMed:37832547). Involved in the inflammatory response to genome instability and double-stranded DNA breaks: acts by localizing to micronuclei arising from genome instability and catalyzing phosphorylation of LMNA at 'Ser-395', priming LMNA for subsequent phosphorylation by CDK1 and micronuclei envelope rupture (PubMed:37788673). The rupture of micronuclear envelope triggers the cGAS-STING pathway thereby activating the type I interferon response and innate immunity (PubMed:37788673).

Positively regulates the restart of stalled replication forks following activation by the KHDC3L-OOEP scaffold complex (By similarity)

Forms a heterodimer with ATRIP, forming the ATR-ATRIP complex (PubMed:11721054, PubMed:12791985, PubMed:14729973, PubMed:15758953, PubMed:21777809). Present in a complex containing ATRIP and RPA-coated single-stranded DNA (PubMed:12791985, PubMed:14729973). Binds to DNA, and to UV-damaged DNA with higher affinity (PubMed:12791985).

Interacts with MSH2 and HDAC2 (PubMed:14657349). Present in a complex containing CHD4 and HDAC2 (PubMed:10545197). Interacts with EEF1E1, the interaction is enhanced by UV irradiation (PubMed:15680327).

Interacts with CLSPN and CEP164 (PubMed:12766152, PubMed:18283122). Interacts with TELO2 and TTI1 (PubMed:20427287, PubMed:20801936, PubMed:20810650). Interacts with BCR-ABL after genotoxic stress (PubMed:15050919).

Interacts with UHRF2; this interaction promotes ATR activation (PubMed:33848395). Interacts (when phosphorylated) with TOPBP1; interaction takes place when ATR is autophosphorylated at Thr-1989, leading to ATR activation by TOPBP1 (PubMed:21705319, PubMed:21777809)

Ubiquitous, with highest expression in testis

Isoform 2 is found in pancreas, placenta and liver but not in heart, testis and ovary

• Seckel syndrome 1 (SCKL1)

  A rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and intellectual disability.

• Cutaneous telangiectasia and cancer syndrome, familial (FCTCS)

  A disease characterized by cutaneous telangiectases in infancy with patchy alopecia over areas of affected skin, thinning of the lateral eyebrows, and mild dental and nail anomalies. Affected individuals are at increased risk of developing oropharyngeal cancer, and other malignancies have been reported as well.