ATR

Summary

Gene Symbol: ATR
Description: ATR serine/threonine kinase
Alias: FCTCS, FRP1, MEC1, SCKL, SCKL1, serine/threonine-protein kinase ATR, FRAP-related protein-1, MEC1, mitosis entry checkpoint 1, homolog, ataxia telangiectasia and Rad3-related protein
Species: human
Products:     ATR

Top Publications

  1. Ward I, Chen J. Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. J Biol Chem. 2001;276:47759-62 pubmed
    ..This response is ATR-dependent but does not require ATM or Hus1...
  2. Myers K, Gagou M, Zuazua Villar P, Rodriguez R, Meuth M. ATR and Chk1 suppress a caspase-3-dependent apoptotic response following DNA replication stress. PLoS Genet. 2009;5:e1000324 pubmed publisher
    The related PIK-like kinases Ataxia-Telangiectasia Mutated (ATM) and ATM- and Rad3-related (ATR) play major roles in the regulation of cellular responses to DNA damage or replication stress...
  3. Chen X, Zhao R, Glick G, Cortez D. Function of the ATR N-terminal domain revealed by an ATM/ATR chimera. Exp Cell Res. 2007;313:1667-74 pubmed
    The ATM and ATR kinases function at the apex of checkpoint signaling pathways...
  4. Tibbetts R, Cortez D, Brumbaugh K, Scully R, Livingston D, Elledge S, et al. Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress. Genes Dev. 2000;14:2989-3002 pubmed
    ..We provide evidence that the kinase responsible for this phosphorylation is the ATM-related kinase, ATR. ATR phosphorylates BRCA1 on six Ser/Thr residues, including Ser 1423, in vitro...
  5. Ozeri Galai E, Schwartz M, Rahat A, Kerem B. Interplay between ATM and ATR in the regulation of common fragile site stability. Oncogene. 2008;27:2109-17 pubmed
    ..response proteins were shown to regulate fragile site stability, including ataxia-telangiectasia and Rad3-related (ATR) and its effector Chk1...
  6. Pichierri P, Rosselli F. The DNA crosslink-induced S-phase checkpoint depends on ATR-CHK1 and ATR-NBS1-FANCD2 pathways. EMBO J. 2004;23:1178-87 pubmed
    ..We found that ICLs activate a branched pathway downstream of the ATR kinase: one branch depending on CHK1 activity and the other on the FANCs-RMN complex...
  7. Azzalin C, Lingner J. The human RNA surveillance factor UPF1 is required for S phase progression and genome stability. Curr Biol. 2006;16:433-9 pubmed
    ..shRNA-mediated depletion of UPF1 causes human cells to arrest early in S phase, inducing an ATR-dependent DNA-damage response...
  8. Hammond E, Denko N, Dorie M, Abraham R, Giaccia A. Hypoxia links ATR and p53 through replication arrest. Mol Cell Biol. 2002;22:1834-43 pubmed
    ..Inhibition of ATR kinase activity substantially reduces hypoxia-induced phosphorylation of p53 protein on serine 15 as well as p53 ..
  9. Foray N, Marot D, Gabriel A, Randrianarison V, Carr A, Perricaudet M, et al. A subset of ATM- and ATR-dependent phosphorylation events requires the BRCA1 protein. EMBO J. 2003;22:2860-71 pubmed
    ..We show here that BRCA1 is required for ATM- and ATR-dependent phosphorylation of p53, c-Jun, Nbs1 and Chk2 following exposure to ionizing or ultraviolet radiation, ..

More Information

Publications98

  1. Matsuoka S, Rotman G, Ogawa A, Shiloh Y, Tamai K, Elledge S. Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro. Proc Natl Acad Sci U S A. 2000;97:10389-94 pubmed
    ..These results suggest that in vivo, Chk2 is directly phosphorylated by ATM in response to IR and that Chk2 is regulated by phosphorylation of the SCD. ..
  2. Shiotani B, Zou L. Single-stranded DNA orchestrates an ATM-to-ATR switch at DNA breaks. Mol Cell. 2009;33:547-58 pubmed publisher
    ATM and ATR are two master checkpoint kinases activated by double-stranded DNA breaks (DSBs). ATM is critical for the initial response and the subsequent ATR activation...
  3. Casper A, Nghiem P, Arlt M, Glover T. ATR regulates fragile site stability. Cell. 2002;111:779-89 pubmed
    ..We demonstrate that the replication checkpoint kinase ATR, but not ATM, is critical for maintenance of fragile site stability...
  4. Gohler T, Sabbioneda S, Green C, Lehmann A. ATR-mediated phosphorylation of DNA polymerase ? is needed for efficient recovery from UV damage. J Cell Biol. 2011;192:219-27 pubmed publisher
    ..after UV irradiation, pol? becomes phosphorylated at Ser601 by the ataxia-telangiectasia mutated and Rad3-related (ATR) kinase...
  5. Shiloh Y. ATM and ATR: networking cellular responses to DNA damage. Curr Opin Genet Dev. 2001;11:71-7 pubmed
    ..The protein kinases ATM and ATR are master controllers of some of these networks, acting either in concert or separately to orchestrate the ..
  6. Mordes D, Glick G, Zhao R, Cortez D. TopBP1 activates ATR through ATRIP and a PIKK regulatory domain. Genes Dev. 2008;22:1478-89 pubmed publisher
    The ATR (ATM and Rad3-related) kinase and its regulatory partner ATRIP (ATR-interacting protein) coordinate checkpoint responses to DNA damage and replication stress. TopBP1 functions as a general activator of ATR...
  7. Liu Q, Guntuku S, Cui X, Matsuoka S, Cortez D, Tamai K, et al. Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Genes Dev. 2000;14:1448-59 pubmed
    ..Overexpression of wild-type Atr enhances, whereas overexpression of the kinase-defective mutant Atr inhibits S345 phosphorylation of Chk1 induced ..
  8. Canman C, Lim D, Cimprich K, Taya Y, Tamai K, Sakaguchi K, et al. Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science. 1998;281:1677-9 pubmed
    ..These observations, along with the fact that phosphorylation of p53 on serine-15 in response to ionizing radiation is reduced in ataxia telangiectasia cells, suggest that ATM is a protein kinase that phosphorylates p53 in vivo. ..
  9. Schmidt D, Schreiber S. Molecular association between ATR and two components of the nucleosome remodeling and deacetylating complex, HDAC2 and CHD4. Biochemistry. 1999;38:14711-7 pubmed
    Ataxia telangiectasia mutated (ATM)- and Rad3-related protein (ATR) is a phosphatidylinositol-kinase (PIK)-related kinase that has been implicated in the response of human cells to multiple forms of DNA damage and may play a role in the ..
  10. Heffernan T, Kawasumi M, Blasina A, Anderes K, Conney A, Nghiem P. ATR-Chk1 pathway inhibition promotes apoptosis after UV treatment in primary human keratinocytes: potential basis for the UV protective effects of caffeine. J Invest Dermatol. 2009;129:1805-15 pubmed publisher
    ..In contrast, siRNA against ataxia-telangiectasia and Rad3-related (ATR) doubled apoptosis after UV through a p53-independent mechanism...
  11. Chini C, Chen J. Human claspin is required for replication checkpoint control. J Biol Chem. 2003;278:30057-62 pubmed
    ..Moreover, Claspin interacts with the checkpoint proteins ATR and Rad9...
  12. Heikkinen K, Mansikka V, Karppinen S, Rapakko K, Winqvist R. Mutation analysis of the ATR gene in breast and ovarian cancer families. Breast Cancer Res. 2005;7:R495-501 pubmed
    ..The ATR (ataxia-telangiectasia- and Rad3-related) kinase is essential for the maintenance of genomic integrity...
  13. Daniel R, Kao G, Taganov K, Greger J, Favorova O, Merkel G, et al. Evidence that the retroviral DNA integration process triggers an ATR-dependent DNA damage response. Proc Natl Acad Sci U S A. 2003;100:4778-83 pubmed
    ..efficient inhibitor of cellular DNA repair, likely through its effects on ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related) kinases...
  14. Smith J, Tho L, Xu N, Gillespie D. The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer. Adv Cancer Res. 2010;108:73-112 pubmed publisher
    ..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...
  15. Zou L, Cortez D, Elledge S. Regulation of ATR substrate selection by Rad17-dependent loading of Rad9 complexes onto chromatin. Genes Dev. 2002;16:198-208 pubmed
    ..Rad17 binds to chromatin prior to damage and is phosphorylated by ATR on chromatin after damage but Rad17's phosphorylation is not required for Rad9 loading onto chromatin...
  16. Blackford A, Patel R, Forrester N, Theil K, Groitl P, Stewart G, et al. Adenovirus 12 E4orf6 inhibits ATR activation by promoting TOPBP1 degradation. Proc Natl Acad Sci U S A. 2010;107:12251-6 pubmed publisher
    ..Ad has therefore evolved a number of strategies to inhibit ATM- and ATR-dependent signaling pathways during infection...
  17. Wu X, Shell S, Yang Z, Zou Y. Phosphorylation of nucleotide excision repair factor xeroderma pigmentosum group A by ataxia telangiectasia mutated and Rad3-related-dependent checkpoint pathway promotes cell survival in response to UV irradiation. Cancer Res. 2006;66:2997-3005 pubmed
    ..repair (NER) factor, could be modulated by checkpoint kinase ataxia-telangiectasia mutated and Rad3-related (ATR) in response to UV irradiation...
  18. Cortez D, Glick G, Elledge S. Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases. Proc Natl Acad Sci U S A. 2004;101:10078-83 pubmed
    ..We describe four lines of evidence that ATM/ATR-dependent (ataxia-telangiectasia-mutated/ATM- and Rad3-related) checkpoint pathways are directly linked to three ..
  19. Qvist P, Huertas P, Jimeno S, Nyegaard M, Hassan M, Jackson S, et al. CtIP Mutations Cause Seckel and Jawad Syndromes. PLoS Genet. 2011;7:e1002310 pubmed publisher
    ..Genetically, it constitutes a heterogeneous condition, with several loci mapped (SCKL1-5) but only three disease genes identified: the ATR, CENPJ, and CEP152 genes that control cellular responses to ..
  20. Choi J, Lindsey Boltz L, Sancar A. Reconstitution of a human ATR-mediated checkpoint response to damaged DNA. Proc Natl Acad Sci U S A. 2007;104:13301-6 pubmed
    ..We show that the damage sensor ATR in the presence of topoisomerase II binding protein 1 (TopBP1) mediator/adaptor protein phosphorylates the Chk1 ..
  21. Zimmerman E, Chen J, Andersen J, Ardon O, Dehart J, Blackett J, et al. Human immunodeficiency virus type 1 Vpr-mediated G2 arrest requires Rad17 and Hus1 and induces nuclear BRCA1 and gamma-H2AX focus formation. Mol Cell Biol. 2004;24:9286-94 pubmed
    ..of replication stress, the damage signal is initiated by the ataxia-telangiectasia-mutated and Rad3-related kinase ATR. We recently demonstrated that the human immunodeficiency virus type 1 (HIV-1) gene product viral protein R (Vpr) ..
  22. Toledo L, Altmeyer M, Rask M, Lukas C, Larsen D, Povlsen L, et al. ATR prohibits replication catastrophe by preventing global exhaustion of RPA. Cell. 2013;155:1088-103 pubmed publisher
    b>ATR, activated by replication stress, protects replication forks locally and suppresses origin firing globally. Here, we show that these functions of ATR are mechanistically coupled...
  23. Derheimer F, O Hagan H, Krueger H, Hanasoge S, Paulsen M, Ljungman M. RPA and ATR link transcriptional stress to p53. Proc Natl Acad Sci U S A. 2007;104:12778-83 pubmed
    ..in the phosphorylation of the Ser-15 site of p53 in a replication protein A (RPA)- and ATM and Rad3-related (ATR)-dependent manner...
  24. Cortez D, Guntuku S, Qin J, Elledge S. ATR and ATRIP: partners in checkpoint signaling. Science. 2001;294:1713-6 pubmed
    The checkpoint kinases ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3 related) transduce genomic stress signals to halt cell cycle progression and promote DNA repair...
  25. Yoshioka K, Yoshioka Y, Hsieh P. ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts. Mol Cell. 2006;22:501-10 pubmed
    ..In an in vitro assay, ATR-ATRIP, but not RPA, is preferentially recruited to O(6)-meG/T mismatches in a MutSalpha- and MutLalpha-dependent ..
  26. Norman J, Mashiba M, McNamara L, Onafuwa Nuga A, Chiari Fort E, Shen W, et al. The antiviral factor APOBEC3G enhances the recognition of HIV-infected primary T cells by natural killer cells. Nat Immunol. 2011;12:975-83 pubmed publisher
    ..Our results show that pathogen-induced deamination of cytidine and the DNA-damage response to virus-mediated repair of the incorporation of uridine enhance the recognition of HIV-infected cells by NK cells. ..
  27. Auclair Y, Rouget R, Affar E, Drobetsky E. ATR kinase is required for global genomic nucleotide excision repair exclusively during S phase in human cells. Proc Natl Acad Sci U S A. 2008;105:17896-901 pubmed publisher
    ..The ataxia telangiectasia and rad-3-related kinase (ATR) is rapidly activated in response to UV-induced replication stress and proceeds to phosphorylate a plethora of ..
  28. Andersen J, Zimmerman E, DeHart J, Murala S, Ardon O, Blackett J, et al. ATR and GADD45alpha mediate HIV-1 Vpr-induced apoptosis. Cell Death Differ. 2005;12:326-34 pubmed
    ..In a previous study, we identified the ataxia telangiectasia-mutated (ATM) and Rad3-related protein (ATR) as a cellular factor that mediates Vpr-induced cell cycle arrest...
  29. Wang Y, Qin J. MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation. Proc Natl Acad Sci U S A. 2003;100:15387-92 pubmed
    ..We report that MSH2 (MutS homolog 2) protein interacts with the ATR (ATM- and Rad3-related) kinase to form a signaling module and regulate the phosphorylation of Chk1 and SMC1 (..
  30. Ward J, Davis Z, DeHart J, Zimmerman E, Bosque A, Brunetta E, et al. HIV-1 Vpr triggers natural killer cell-mediated lysis of infected cells through activation of the ATR-mediated DNA damage response. PLoS Pathog. 2009;5:e1000613 pubmed publisher
    ..by Vpr is also dependent on activation of the DNA damage sensor, ataxia telangiectasia and rad-3-related kinase (ATR). When T-cell blasts are infected with a vpr-deficient HIV-1, NK cells are impaired in killing the infected cells...
  31. Goodship J, Gill H, Carter J, Jackson A, Splitt M, Wright M. Autozygosity mapping of a seckel syndrome locus to chromosome 3q22. 1-q24. Am J Hum Genet. 2000;67:498-503 pubmed
    ..72. All five affected individuals were homozygous for the same allele, for two adjacent polymorphic markers within the region segregating with the disease, narrowing the region to 12 cM. ..
  32. Carson C, Orazio N, Lee D, Suh J, Bekker Jensen S, Araujo F, et al. Mislocalization of the MRN complex prevents ATR signaling during adenovirus infection. EMBO J. 2009;28:652-62 pubmed publisher
    The protein kinases ataxia-telangiectasia mutated (ATM) and ATM-Rad3 related (ATR) are activated in response to DNA damage, genotoxic stress and virus infections...
  33. Tibbetts R, Brumbaugh K, Williams J, Sarkaria J, Cliby W, Shieh S, et al. A role for ATR in the DNA damage-induced phosphorylation of p53. Genes Dev. 1999;13:152-7 pubmed
    ..In this report we provide evidence that the ATM-Rad3-related protein ATR regulates phosphorylation of Ser-15 in DNA-damaged cells...
  34. Dart D, Adams K, Akerman I, Lakin N. Recruitment of the cell cycle checkpoint kinase ATR to chromatin during S-phase. J Biol Chem. 2004;279:16433-40 pubmed
    The ataxia telangiectasia-mutated (ATM) and Rad3-related kinase (ATR) is a central component of the cell cycle checkpoint machinery required to induce cell cycle arrest in response to DNA damage...
  35. Pichierri P, Rosselli F, Franchitto A. Werner's syndrome protein is phosphorylated in an ATR/ATM-dependent manner following replication arrest and DNA damage induced during the S phase of the cell cycle. Oncogene. 2003;22:1491-500 pubmed
    ..Here, we show that WRN is phosphorylated through an ATR/ATM dependent pathway in response to replication blockage...
  36. Andersen J, Le Rouzic E, Planelles V. HIV-1 Vpr: mechanisms of G2 arrest and apoptosis. Exp Mol Pathol. 2008;85:2-10 pubmed publisher
    ..Expression of Vpr, in particular, leads to cell cycle arrest in G(2), followed by apoptosis. Here we summarize our current understanding of Vpr biology with a focus on Vpr-induced G(2) arrest and apoptosis. ..
  37. Ward I, Minn K, Chen J. UV-induced ataxia-telangiectasia-mutated and Rad3-related (ATR) activation requires replication stress. J Biol Chem. 2004;279:9677-80 pubmed
    Ataxia-telangiectasia-mutated and Rad3-related (ATR) plays an essential role in the maintenance of genome integrity and cell viability...
  38. Zimmerman E, Sherman M, Blackett J, Neidleman J, Kreis C, Mundt P, et al. Human immunodeficiency virus type 1 Vpr induces DNA replication stress in vitro and in vivo. J Virol. 2006;80:10407-18 pubmed
    ..certain forms of DNA damage, specifically activation of the ataxia telangiectasia mutated and Rad3-related kinase, ATR. However, evidence that Vpr function is relevant in vivo or in the context of viral infection is still lacking...
  39. Rendtlew Danielsen J, Larsen D, Schou K, Freire R, Falck J, Bartek J, et al. HCLK2 is required for activity of the DNA damage response kinase ATR. J Biol Chem. 2009;284:4140-7 pubmed publisher
    b>ATR is a protein kinase that orchestrates the cellular response to replication problems and DNA damage. HCLK2 has previously been reported to stabilize ATR and Chk1...
  40. Jiang M, Zhao L, Gamez M, Imperiale M. Roles of ATM and ATR-mediated DNA damage responses during lytic BK polyomavirus infection. PLoS Pathog. 2012;8:e1002898 pubmed publisher
    ..Our results showed that both the ataxia-telangiectasia mutated (ATM)- and ATM and Rad-3-related (ATR)-mediated DDR were activated during BKPyV infection, accompanied by the accumulation of polyploid cells...
  41. Cotta Ramusino C, McDonald E, Hurov K, Sowa M, Harper J, Elledge S. A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1 interacting protein required for ATR signaling. Science. 2011;332:1313-7 pubmed publisher
    ..cell cycle arrest and uncovered a critical role for Fanconi anemia and homologous recombination proteins in ATR (ataxia telangiectasia and Rad3-related) signaling...
  42. Li Z, Musich P, Serrano M, Dong Z, Zou Y. XPA-mediated regulation of global nucleotide excision repair by ATR Is p53-dependent and occurs primarily in S-phase. PLoS ONE. 2011;6:e28326 pubmed publisher
    ..Here we demonstrate that nucleotide excision repair (NER) is regulated by the ATR/p53 checkpoint via modulation of XPA nuclear import and that this regulation occurs in a cell cycle-dependent ..
  43. Wang H, Wang H, Powell S, Iliakis G, Wang Y. ATR affecting cell radiosensitivity is dependent on homologous recombination repair but independent of nonhomologous end joining. Cancer Res. 2004;64:7139-43 pubmed
    b>ATR is one of the most important checkpoint proteins in mammalian cells responding to DNA damage. Cells defective in normal ATR activity are sensitive to ionizing radiation (IR)...
  44. Mannino J, Kim W, Wernick M, Nguyen S, Braquet R, Adamson A, et al. Evidence for alternate splicing within the mRNA transcript encoding the DNA damage response kinase ATR. Gene. 2001;272:35-43 pubmed
    ..We have determined that the transcript encoding the PIK-like protein ATR undergoes alternate splicing within the region of the mRNA encoding its non-catalytic domain...
  45. Shell S, Li Z, Shkriabai N, Kvaratskhelia M, Brosey C, Serrano M, et al. Checkpoint kinase ATR promotes nucleotide excision repair of UV-induced DNA damage via physical interaction with xeroderma pigmentosum group A. J Biol Chem. 2009;284:24213-22 pubmed publisher
    ..However, this process is still poorly understood. Nucleotide excision repair (NER) and the ATR-dependent cell cycle checkpoint are the major pathways responsible for repair of UV-induced DNA damage...
  46. Hammond E, Dorie M, Giaccia A. Inhibition of ATR leads to increased sensitivity to hypoxia/reoxygenation. Cancer Res. 2004;64:6556-62 pubmed
    ..S-phase arrest results in regions of single-stranded DNA in stalled replication forks and signals the activation of ATR. S-phase cells represent the most sensitive phase of the cell cycle to the stress of hypoxia/reoxygenation...
  47. Helt C, Cliby W, Keng P, Bambara R, O Reilly M. Ataxia telangiectasia mutated (ATM) and ATM and Rad3-related protein exhibit selective target specificities in response to different forms of DNA damage. J Biol Chem. 2005;280:1186-92 pubmed
    The ataxia telangiectasia mutated (ATM) and ATR (ATM and Rad3-related) protein kinases exert cell cycle delay, in part, by phosphorylating Checkpoint kinase (Chk) 1, Chk2, and p53...
  48. Alderton G, Joenje H, Varon R, Børglum A, Jeggo P, O Driscoll M. Seckel syndrome exhibits cellular features demonstrating defects in the ATR-signalling pathway. Hum Mol Genet. 2004;13:3127-38 pubmed
    ..in the developmental disorder, Seckel syndrome, is a mutation in ataxia telangiectasia and Rad3-related protein (ATR)...
  49. Bao S, Tibbetts R, Brumbaugh K, Fang Y, Richardson D, Ali A, et al. ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses. Nature. 2001;411:969-74 pubmed
    ..a direct regulatory linkage between the human Rad17 homologue (hRad17) and the checkpoint kinases, ATM and ATR. Treatment of human cells with genotoxic agents induced ATM/ATR-dependent phosphorylation of hRad17 at Ser 635 and ..
  50. Tomimatsu N, Mukherjee B, Burma S. Distinct roles of ATR and DNA-PKcs in triggering DNA damage responses in ATM-deficient cells. EMBO Rep. 2009;10:629-35 pubmed publisher
    ..of ataxia telangiectasia mutated (ATM) and indirect activation of ataxia telangiectasia and Rad3 related (ATR) in an ATM/Mre11/cell-cycle-dependent manner...
  51. Andersen J, Dehart J, Zimmerman E, Ardon O, Kim B, Jacquot G, et al. HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT. PLoS Pathog. 2006;2:e127 pubmed
    ..We previously identified the DNA damage-signaling protein ATR as the cellular factor that mediates Vpr-induced G2 arrest and apoptosis...
  52. Mohni K, Livingston C, Cortez D, Weller S. ATR and ATRIP are recruited to herpes simplex virus type 1 replication compartments even though ATR signaling is disabled. J Virol. 2010;84:12152-64 pubmed publisher
    Although the herpes simplex virus type 1 (HSV-1) genome might be expected to induce a DNA damage response, the ATR kinase is not activated in infected cells...
  53. Lindsey Boltz L, Serçin O, Choi J, Sancar A. Reconstitution of human claspin-mediated phosphorylation of Chk1 by the ATR (ataxia telangiectasia-mutated and rad3-related) checkpoint kinase. J Biol Chem. 2009;284:33107-14 pubmed publisher
    b>ATR (ATM and Rad3-related) initiates a DNA damage signaling pathway in human cells upon DNA damage induced by UV and UV-mimetic agents and in response to inhibition of DNA replication...
  54. Zhang X, Zhao C, Ma Z. The increase of cell-membranous phosphatidylcholines containing polyunsaturated fatty acid residues induces phosphorylation of p53 through activation of ATR. J Cell Sci. 2007;120:4134-43 pubmed
    ..This phosphorylation requires the kinase ataxia-telangiectasia and Rad-3-related (ATR) but not the ataxia-telangiectasia-mutated (ATM) kinase...
  55. Orba Y, Suzuki T, Makino Y, Kubota K, Tanaka S, Kimura T, et al. Large T antigen promotes JC virus replication in G2-arrested cells by inducing ATM- and ATR-mediated G2 checkpoint signaling. J Biol Chem. 2010;285:1544-54 pubmed publisher
    ..cells expressing TAg accumulate in the G(2) phase of the cell cycle as a result of the activation of ATM- and ATR-mediated G(2) checkpoint pathways...
  56. Nam E, Zhao R, Cortez D. Analysis of mutations that dissociate G(2) and essential S phase functions of human ataxia telangiectasia-mutated and Rad3-related (ATR) protein kinase. J Biol Chem. 2011;286:37320-7 pubmed publisher
    b>ATR (ataxia telangiectasia-mutated and Rad3-related) contains 16 conserved candidate autophosphorylation sites that match its preferred S/TQ consensus...
  57. Jones G, Reaper P, Pettitt A, Sherrington P. The ATR-p53 pathway is suppressed in noncycling normal and malignant lymphocytes. Oncogene. 2004;23:1911-21 pubmed
    ..Since other forms of DNA damage activate p53 via ATR, a kinase closely related to ATM, abnormalities of the ATR-p53 pathway also have the potential to result in p53 ..
  58. Andreassen P, D Andrea A, Taniguchi T. ATR couples FANCD2 monoubiquitination to the DNA-damage response. Genes Dev. 2004;18:1958-63 pubmed
    ..Here, we demonstrate that the ATR checkpoint kinase and RPA1 are required for efficient FANCD2 monoubiquitination...
  59. Shigechi T, Tomida J, Sato K, Kobayashi M, Eykelenboom J, Pessina F, et al. ATR-ATRIP kinase complex triggers activation of the Fanconi anemia DNA repair pathway. Cancer Res. 2012;72:1149-56 pubmed publisher
    b>ATR kinase activates the S-phase checkpoint when replication forks stall at sites of DNA damage...
  60. Lai M, Zimmerman E, Planelles V, Chen J. Activation of the ATR pathway by human immunodeficiency virus type 1 Vpr involves its direct binding to chromatin in vivo. J Virol. 2005;79:15443-51 pubmed
    ..Vpr (viral protein R) arrests cells in the G2 phase of the cell cycle, a process that requires activation of the ATR (ataxia-telangiectasia and Rad3-related) pathway...
  61. Zhu W, Dutta A. An ATR- and BRCA1-mediated Fanconi anemia pathway is required for activating the G2/M checkpoint and DNA damage repair upon rereplication. Mol Cell Biol. 2006;26:4601-11 pubmed
    ..Both ATR and BRCA1 are required to activate the FA pathway...
  62. Sarkaria J, Tibbetts R, Busby E, Kennedy A, Hill D, Abraham R. Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin. Cancer Res. 1998;58:4375-82 pubmed
    ..protein kinase (DNA-PK), ataxia telangiectasia mutated (ATM) and the ataxia- and Rad3-related protein (ATR), are potential targets for the radiosensitizing effect of wortmannin...
  63. Stauffer D, Chang B, Huang J, Dunn A, Thayer M. p300/CREB-binding protein interacts with ATR and is required for the DNA replication checkpoint. J Biol Chem. 2007;282:9678-87 pubmed
    ..We demonstrate that complexes containing p300/CBP and ATR can be detected in mammalian cells, and that the downstream kinase CHK1 fails to be phosphorylated in response to ..
  64. Durocher F, Labrie Y, Soucy P, Sinilnikova O, Labuda D, Bessette P, et al. Mutation analysis and characterization of ATR sequence variants in breast cancer cases from high-risk French Canadian breast/ovarian cancer families. BMC Cancer. 2006;6:230 pubmed
    Ataxia telangiectasia-mutated and Rad3-related (ATR) is a member of the PIK-related family which plays, along with ATM, a central role in cell-cycle regulation...
  65. Wallace N, Robinson K, Howie H, Galloway D. HPV 5 and 8 E6 abrogate ATR activity resulting in increased persistence of UVB induced DNA damage. PLoS Pathog. 2012;8:e1002807 pubmed publisher
    ..We further demonstrate that HPV 5 and 8 E6 expression reduces the mRNA and protein levels of ATR, a PI3 kinase family member that plays a key role in UV damage signaling, but that these levels remain unperturbed ..
  66. Hammond E, Dorie M, Giaccia A. ATR/ATM targets are phosphorylated by ATR in response to hypoxia and ATM in response to reoxygenation. J Biol Chem. 2003;278:12207-13 pubmed
    The ATR kinase phosphorylates both p53 and Chk1 in response to extreme hypoxia (oxygen concentrations of less than 0.02%)...
  67. Bernardi R, Scaglioni P, Bergmann S, Horn H, Vousden K, Pandolfi P. PML regulates p53 stability by sequestering Mdm2 to the nucleolus. Nat Cell Biol. 2004;6:665-72 pubmed
    ..In addition, we found that the nucleolar localization of PML is dependent on ATR activation and phosphorylation of PML by ATR...
  68. Choi J, Lindsey Boltz L, Kemp M, Mason A, Wold M, Sancar A. Reconstitution of RPA-covered single-stranded DNA-activated ATR-Chk1 signaling. Proc Natl Acad Sci U S A. 2010;107:13660-5 pubmed publisher
    b>ATR kinase is a critical upstream regulator of the checkpoint response to various forms of DNA damage...
  69. Richard J, Sindhu S, Pham T, Belzile J, Cohen E. HIV-1 Vpr up-regulates expression of ligands for the activating NKG2D receptor and promotes NK cell-mediated killing. Blood. 2010;115:1354-63 pubmed publisher
    ..HIV-1 Vpr activates the DNA damage/stress-sensing ATR kinase and promotes G(2) cell-cycle arrest, conditions known to up-regulate NKG2D ligands...
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    ..The ATM and Rad3-related protein (ATR) is a member of the phosphatidylinositol 3 kinase-related family of protein kinases that play a major role in ..
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    ..of RPA70 and RPA32, subunits of the ssDNA-binding protein, and the ataxia-telangiectasia and Rad3-related (ATR) substrate Rad17 and its phosphorylated form were increased on CNDAC exposure, suggesting activation of ATR kinase...
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    ..We further demonstrate that this role is mediated through BID phosphorylation by the DNA-damage kinase ATM. These results establish a link between proapoptotic Bid and the DNA-damage response...
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    ..These results implicate BID as an ATM effector and raise the possibility that proapoptotic BID may also play a prosurvival role important for S phase arrest. ..
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    ..present study, we examined a recently identified DNA damage-signaling protein, the ATM- and Rad3-related protein, ATR, for its potential role in the induction of G2 arrest by Vpr...
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    ..29 Mbp and 150.37 Mbp). The gene encoding ataxia-telangiectasia and Rad3-related protein (ATR) maps to this region...
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    ..ATM), DNA-dependent protein kinase (DNA-PK), and ataxia telangiectasia-mutated and Rad3-related (ATR) signal through multiple pathways to promote genome maintenance...
  78. Lindsey Boltz L, Sancar A. Tethering DNA damage checkpoint mediator proteins topoisomerase IIbeta-binding protein 1 (TopBP1) and Claspin to DNA activates ataxia-telangiectasia mutated and RAD3-related (ATR) phosphorylation of checkpoint kinase 1 (Chk1). J Biol Chem. 2011;286:19229-36 pubmed publisher
    The ataxia-telangiectasia mutated and RAD3-related (ATR) kinase initiates DNA damage signaling pathways in human cells after DNA damage such as that induced upon exposure to ultraviolet light by phosphorylating many effector proteins ..
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    b>ATR, a phosphatidylinositol kinase-related protein homologous to ataxia telangiectasia mutated (ATM), is important for the survival of human cells following many forms of DNA damage...
  80. Zhao H, Piwnica Worms H. ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1. Mol Cell Biol. 2001;21:4129-39 pubmed
    ..Serines 317 and 345 were identified as sites of phosphorylation in vivo, and ATR (the ATM- and Rad3-related protein kinase) phosphorylated both of these sites in vitro...
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    ..20; 95% CI, 1.07-1.36; P trend = 0.002). In summary, there was little evidence of breast cancer susceptibility with any of the SNPs studied, but larger studies would be needed to confirm subgroup effects. ..
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    ..Pretreatment of normal and AT fibroblasts with caffeine or UCN-01, inhibitors of ATR (AT mutated and Rad3 related) and Chk1, respectively, abolished the S checkpoint response to UVC...
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    The ATR-ATRIP kinase complex regulates cellular responses to DNA damage and replication stress...
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    Upon DNA damage, replication is inhibited by the S-phase checkpoint. ATR (ataxia telangiectasia mutated- and Rad3-related) is specifically involved in the inhibition of replicon initiation when cells are treated with DNA damage-inducing ..
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    Ataxia-telangiectasia mutated (ATM), ataxia-telangiectasia and Rad3-related (ATR) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are members of the phosphoinositide-3-kinase-related protein kinase (PIKK) family, and are ..
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    The ataxia-telangiectasia mutated and rad3-related (ATR) kinase orchestrates cellular responses to DNA damage and replication stress. Complete loss of ATR function leads to chromosomal instability and cell death...
  87. Herbig U, Jobling W, Chen B, Chen D, Sedivy J. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell. 2004;14:501-13 pubmed
    ..b>ATR kinase appears to play a minor role in normal cells but in the absence of ATM elicited a delayed G2 phase arrest...
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    b>ATR is a key regulator of checkpoint responses to incompletely replicated and damaged DNA, but the mechanisms underlying control of its kinase activity are unknown...
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    b>ATR associates with the regulatory protein ATRIP that has been proposed to localize ATR to sites of DNA damage through an interaction with single-stranded DNA (ssDNA) coated with replication protein A (RPA)...