Ataxia telangiectasia & Rad3-related (ATR) or FRAP-related protein-1 (FRP1)

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Function

serine/threonine kinase
recognizes the substrate consensus sequence [ST]-Q
activates checkpoint signaling upon genotoxic stresses
- ionizing radiation
- ultraviolet light
- DNA replication stalling
role as DNA damage sensor
Binds to DNA, & to UV- damaged DNA with higher affinity
inhibits DNA replication & mitosis
promotes DNA repair, DNA recombination, apoptosis
phosphorylates BRCA1,CHEK1, H2AFX, MCM2, RAD17, RPA2, SMC1 & p53 which collectively inhibit DNA replication & mitosis & promote DNA repair, recombination & apoptosis
phosphorylates Ser-139 of histone variant H2AX/H2AFX at sites of DNA damage, thus regulating DNA damage response
autophosphorylates in vitro
required for FANCD2 ubiquitination
maintenance of fragile site stability & efficient regulation of centrosome duplication
forms an heterodimer with ATRIP
complexes with CHD4 and HDAC2
interacts with BCR-ABL after genotoxic stress
interacts with EEF1E1 & CLSPN (enhanced by UV irradiation)
interacts with RAD17, MSH2 ,HDAC2
present in a complex containing CHD4 & HDAC2
present in a complex containing ATRIP & RPA-coated single-stranded DNA
activated by DNA
inhibited by BCR-ABL oncogene
slightly activated by ATRIP, forms heterodimer with ATRIP

nucleus
depending on the cell type, can also be found in PML nuclear bodies
recruited to chromatin during S-phase
redistributes to discrete nuclear foci upon DNA damage, hypoxia or replication fork stalling

ubiquitous, with highest expression in testis.
Recruited to chromatin during S-phase.
Redistributes to discrete nuclear foci upon
- DNA damage,
- hypoxia
- replication fork stalling.