Distinct but Concerted Roles of ATR, DNA-PK, and Chk1 in Countering Replication Stress during S Phase

Lessons from hereditary colorectal cancer

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The DNA Damage Response: Making It Safe to Play with Knives

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Sensing DNA Damage Through ATRIP Recognition of RPA-ssDNA Complexes

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Causes and consequences of replication stress

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Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions

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An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer

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Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints

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ATR: an essential regulator of genome integrity

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Chk1 is an essential kinase that is regulated by Atr and required for the G ₂ /M DNA damage checkpoint

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DNA Damage Sensing by the ATM and ATR Kinases

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ATR-Mediated Checkpoint Pathways Regulate Phosphorylation and Activation of Human Chk1

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ATR and ATRIP: Partners in Checkpoint Signaling

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<i>ATR</i> disruption leads to chromosomal fragmentation and early embryonic lethality

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Cellular Targets for Activation by the E2F1 Transcription Factor Include DNA Synthesis- and G 1 /S-Regulatory Genes

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Epigenetic and genetic features of 24 colon cancer cell lines

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ATR prohibits replication catastrophe by preventing global exhaustion of RPA

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Deletion of the Developmentally Essential Gene ATR in Adult Mice Leads to Age-Related Phenotypes and Stem Cell Loss

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A Suppressor of Two Essential Checkpoint Genes Identifies a Novel Protein that Negatively Affects dNTP Pools

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Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR

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Inhibition of Human Chk1 Causes Increased Initiation of DNA Replication, Phosphorylation of ATR Targets, and DNA Breakage

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Prevalence of the Alternative Lengthening of Telomeres Telomere Maintenance Mechanism in Human Cancer Subtypes

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Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors

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A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations

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Degradation of Cdc25A by β-TrCP during S phase and in response to DNA damage

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Selective induction of E2F1 in response to DNA damage, mediated by ATM-dependent phosphorylation.

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ATR phosphorylates SMARCAL1 to prevent replication fork collapsePreprint

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Cyclin F-Mediated Degradation of Ribonucleotide Reductase M2 Controls Genome Integrity and DNA Repair

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DNA Replication TimingPreprint

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ATR and ATM regulate the timing of DNA replication origin firing

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Fission yeast genes involved in coupling mitosis to completion of DNA replication.Preprint

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Exploiting oncogene-induced replicative stress for the selective killing of Myc-driven tumors

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An ATR- and Cdc7-Dependent DNA Damage Checkpoint that Inhibits Initiation of DNA Replication

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A mouse model of ATR-Seckel shows embryonic replicative stress and accelerated aging

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How do Cdc7 and cyclin-dependent kinases trigger the initiation of chromosome replication in eukaryotic cells?Preprint

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SCF^β-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase

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Chk1 promotes replication fork progression by controlling replication initiation

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Cyclin-Dependent Kinase Suppression by WEE1 Kinase Protects the Genome through Control of Replication Initiation and Nucleotide Consumption

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ATR: a master conductor of cellular responses to DNA replication stress

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Chk1 regulates the density of active replication origins during the vertebrate S phase

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Combining ATR Suppression with Oncogenic Ras Synergistically Increases Genomic Instability, Causing Synthetic Lethality or Tumorigenesis in a Dosage-Dependent Manner

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Discovery of 4-{4-[(3 R )-3-Methylmorpholin-4-yl]-6-[1-(methylsulfonyl)cyclopropyl]pyrimidin-2-yl}-1 H -indole (AZ20): A Potent and Selective Inhibitor of ATR Protein Kinase with Monotherapy in Vivo Antitumor Activity

Foote, K. M., Blades, K., Cronin, A. S., Fillery, S. M., Guichard, S. S., Hassall, L. A., Hickson, I., Jacq, X., Jewsbury, P. J., McGuire, T. M., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm301859s · Cited by 221 · see citing works

Phase I dose-escalation study of AZD7762, a checkpoint kinase inhibitor, in combination with gemcitabine in US patients with advanced solid tumors

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Oncogenes induce genotoxic stress by mitotic processing of unusual replication intermediates

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Chk1 Requirement for High Global Rates of Replication Fork Progression during Normal Vertebrate S Phase

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Oncogenic stress sensitizes murine cancers to hypomorphic suppression of ATR

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Identification of RNR4 , Encoding a Second Essential Small Subunit of Ribonucleotide Reductase in Saccharomyces cerevisiae

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ATR Inhibitors VE-821 and VX-970 Sensitize Cancer Cells to Topoisomerase I Inhibitors by Disabling DNA Replication Initiation and Fork Elongation Responses

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Mec1 Is One of Multiple Kinases that Prime the Mcm2-7 Helicase for Phosphorylation by Cdc7

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Mouse ribonucleotide reductase R2 protein: A new target for anaphase-promoting complex-Cdh1-mediated proteolysis

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Distinct modes of ATR activation after replication stress and DNA double‐strand breaks in Caenorhabditis elegans

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Implication of Checkpoint Kinase-dependent Up-regulation of Ribonucleotide Reductase R2 in DNA Damage Response

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Activation of dormant origins of DNA replication in budding yeastPreprint

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ATR and H2AX cooperate in maintaining genome stability under replication stress

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Structure-Specific DNA Endonuclease Mus81/Eme1 Generates DNA Damage Caused by Chk1 Inactivation

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Phosphoproteomics Reveals Distinct Modes of Mec1/ATR Signaling during DNA Replication

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Phase I and Pharmacologic Trial of Cytosine Arabinoside with the Selective Checkpoint 1 Inhibitor Sch 900776 in Refractory Acute Leukemias

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Claspin Promotes Normal Replication Fork Rates in Human Cells

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RNF4 and PLK1 are required for replication fork collapse in ATR-deficient cellsPreprint

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ATR Activates the S-M Checkpoint during Unperturbed Growth to Ensure Sufficient Replication Prior to Mitotic Onset

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A phase II study of UCN-01 in combination with irinotecan in patients with metastatic triple negative breast cancer

Ma, C. X., Ellis, M. J., Petroni, G. R., Guo, Z., Cai, S.-R., Ryan, C. E., Lockhart, A. C., Naughton, M. J., Pluard, T., Brenin, C. M., et al. (2012) · Breast Cancer Research and Treatment · doi:10.1007/s10549-012-2378-9 · Cited by 111 · see citing works

Phase I, dose-escalation study of AZD7762 alone and in combination with gemcitabine in Japanese patients with advanced solid tumours

Seto, T., Esaki, T., Hirai, F., Arita, S., Nosaki, K., Makiyama, A., Kometani, T., Fujimoto, C., Hamatake, M., Takeoka, H., et al. (2013) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-013-2234-6 · Cited by 104 · see citing works

Suppression of Genome Instability in pRB-Deficient Cells by Enhancement of Chromosome Cohesion

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ATR maintains select progenitors during nervous system development

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Phenotypic Analysis of Separation-of-Function Alleles of MEI-41, Drosophila ATM/ATR

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Essential role for Cdk2 inhibitory phosphorylation during replication stress revealed by a human Cdk2 knockin mutation

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IncreasedRrm2gene dosage reduces fragile site breakage and prolongs survival of ATR mutant micePreprint

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DNA damage‐induced CHK1 autophosphorylation at Ser296 is regulated by an intramolecular mechanism

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DNA structure-specific priming of ATR activation by DNA-PKcs

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Telomerase activity in 144 brain tumours

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ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response

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Targeting the DNA Damage Response in Cancer

O’Connor, M. J. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.10.040 · Cited by 1,551 · see citing works

The essential kinase ATR: ensuring faithful duplication of a challenging genome

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Targeting DNA Repair in Cancer: Beyond PARP Inhibitors

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Hallmarks of DNA replication stress

Saxena, S., & Zou, L. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.05.004 · Cited by 442 · see citing works

Mechanisms of Oncogene-Induced Replication Stress: Jigsaw Falling into Place

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ATR/CHK1 inhibitors and cancer therapy

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Therapy resistance: opportunities created by adaptive responses to targeted therapies in cancer

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AZD7648 is a potent and selective DNA-PK inhibitor that enhances radiation, chemotherapy and olaparib activity

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Targeting ATR in cancer

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A mitosis-specific and R loop–driven ATR pathway promotes faithful chromosome segregation

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The impact of replication stress on replication dynamics and DNA damage in vertebrate cells

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PRIMPOL-Mediated Adaptive Response Suppresses Replication Fork Reversal in BRCA-Deficient Cells

Quinet, A., Tirman, S., Jackson, J., Šviković, S., Lemacon, D. S., Carvajal-Maldonado, D., González‐Acosta, D., Vessoni, A. T., Cybulla, E., Wood, M. D., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.10.008 · Cited by 259 · see citing works

Sequential Therapy with PARP and WEE1 Inhibitors Minimizes Toxicity while Maintaining Efficacy

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Replication Catastrophe: When a Checkpoint Fails because of Exhaustion

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APOBEC3A and APOBEC3B Activities Render Cancer Cells Susceptible to ATR Inhibition

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The synthetic lethality of targeting cell cycle checkpoints and PARPs in cancer treatment

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ATM Deficiency Generating Genomic Instability Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Therapy-Induced DNA Damage

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Ca2+-Stimulated AMPK-Dependent Phosphorylation of Exo1 Protects Stressed Replication Forks from Aberrant Resection

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RP-3500: A Novel, Potent, and Selective ATR Inhibitor that is Effective in Preclinical Models as a Monotherapy and in Combination with PARP Inhibitors

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Acetylation regulates ribonucleotide reductase activity and cancer cell growth

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A Surveillance Mechanism Ensures Repair of DNA Lesions during Zygotic Reprogramming

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Identification of a Molecularly-Defined Subset of Breast and Ovarian Cancer Models that Respond to WEE1 or ATR Inhibition, Overcoming PARP Inhibitor Resistance

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Targeting Wee1 kinase as a therapeutic approach in Hematological Malignancies

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Targeting the kinase activities of ATR and ATM exhibits therapeutic potential in a mouse model of MLL-rearranged AML

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Key Proteins of Replication Stress Response and Cell Cycle Control as Cancer Therapy Targets

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Modulation of the DNA damage response during the life cycle of human papillomaviruses

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A patient-derived-xenograft platform to study BRCA-deficient ovarian cancers

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53BP1 Mediates ATR-Chk1 Signaling and Protects Replication Forks under Conditions of Replication Stress

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Differential Activity of ATR and WEE1 Inhibitors in a Highly Sensitive Subpopulation of DLBCL Linked to Replication Stress

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S-phase checkpoint regulations that preserve replication and chromosome integrity upon dNTP depletion

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ATR inhibition facilitates targeting of leukemia dependence on convergent nucleotide biosynthetic pathways

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Radiation-dose-dependent functional synergisms between ATM, ATR and DNA-PKcs in checkpoint control and resection in G2-phase

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ATR promotes clearance of damaged DNA and damaged cells by rupturing micronuclei

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Sustained E2F-Dependent Transcription Is a Key Mechanism to Prevent Replication-Stress-Induced DNA Damage

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Checkpoint Kinase Rad53 Couples Leading- and Lagging-Strand DNA Synthesis under Replication Stress

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A wake-up call for cancer DNA damage: the role of Schlafen 11 (SLFN11) across multiple cancers

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Mec1 Is Activated at the Onset of Normal S Phase by Low-dNTP Pools Impeding DNA Replication

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HPV31 utilizes the ATR-Chk1 pathway to maintain elevated RRM2 levels and a replication-competent environment in differentiating Keratinocytes

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Mechanisms responsible for the synergistic antileukemic interactions between ATR inhibition and cytarabine in acute myeloid leukemia cells

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hDNA2 nuclease/helicase promotes centromeric DNA replication and genome stability

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Checkpoint Kinase 1 Inhibition Enhances Cisplatin Cytotoxicity and Overcomes Cisplatin Resistance in SCLC by Promoting Mitotic Cell Death

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A landscape of response to drug combinations in non-small cell lung cancer

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E2F1 proteolysis via SCF‐cyclin F underlies synthetic lethality between cyclin F loss and Chk1 inhibition

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Combined ATR and DNA-PK Inhibition Radiosensitizes Tumor Cells Independently of Their p53 Status

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Harnessing DNA Replication Stress for Novel Cancer Therapy

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Progerin sequestration of PCNA promotes replication fork collapse and mislocalization of XPA in laminopathy‐related progeroid syndromes

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Replication Stress Defines Distinct Molecular Subtypes Across Cancers

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ATR-mediated proteome remodeling is a major determinant of homologous recombination capacity in cancer cells

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Impact of Replication Stress in Human Papillomavirus Pathogenesis

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SMARCA4 deficiency-associated heterochromatin induces intrinsic DNA replication stress and susceptibility to ATR inhibition in lung adenocarcinoma

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MMB-FOXM1-driven premature mitosis is required for CHK1 inhibitor sensitivity

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Kinase-dead ATR differs from ATR loss by limiting the dynamic exchange of ATR and RPA

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RRM2 enhances MYCN-driven neuroblastoma formation and acts as a synergistic target with CHK1 inhibition

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The mTOR pathway: Implications for DNA replication

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Co-regulation and function of FOXM1/RHNO1 bidirectional genes in cancer

Barger, C. J., Chee, L., Albahrani, M., Muñoz-Trujillo, C., Boghean, L., Branick, C., Odunsi, K. O., Drapkin, R., Zou, L., & Karpf, A. R. (2021) · eLife · doi:10.7554/elife.55070 · Cited by 47 · see citing works

ATR protects ongoing and newly assembled DNA replication forks through distinct mechanisms

Leung, W., Simoneau, A., Saxena, S., Jackson, J., Patel, P. S., Limbu, M., Vindigni, A., & Zou, L. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112792 · Cited by 45 · see citing works

Inhibition of ATR acutely sensitizes acute myeloid leukemia cells to nucleoside analogs that target ribonucleotide reductase

Fordham, S. E., Blair, H. J., Elstob, C. J., Plummer, R., Drew, Y., Curtin, N. J., Heidenreich, O. T., Pal, D., Jamieson, D., Park, C., et al. (2018) · Blood Advances · doi:10.1182/bloodadvances.2017015214 · Cited by 45 · see citing works

RB1 loss overrides PARP inhibitor sensitivity driven by RNASEH2B loss in prostate cancer

Miao, C., Tsujino, T., Takai, T., Gui, F., Tsutsumi, T., Sztupinszki, Z. M., Wang, Z., Azuma, H., Szállási, Z., Mouw, K. W., et al. (2022) · Science Advances · doi:10.1126/sciadv.abl9794 · Cited by 45 · see citing works

Evidence That the ATR/Chk1 Pathway Maintains Normal Replication Fork Progression during Unperturbed S Phase

Petermann, E., & Caldecott, K. W. (2006) · Cell Cycle · doi:10.4161/cc.5.19.3256 · Cited by 163 · see citing works

Sensitivity of cells to ATR and CHK1 inhibitors requires hyperactivation of CDK2 rather than endogenous replication stress or ATM dysfunction

Ditano, J. P., Donahue, K. L., Tafe, L. J., McCleery, C. F., & Eastman, A. R. (2021) · Scientific Reports · doi:10.1038/s41598-021-86490-x · Cited by 13 · see citing works

ATR and DNA-PK/CHK1 Elicit Distinct Responses in Cancer Cells

(2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-rw2015-184

Inhibition of ATR-dependent feedback activation of Chk1 sensitises cancer cells to Chk1 inhibitor monotherapy

Massey, A. J. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.09.024 · Cited by 23 · see citing works

ATR and Chk1 Suppress a Caspase-3–Dependent Apoptotic Response Following DNA Replication Stress

Myers, K. N., Gagou, M. E., Zuazua‐Villar, P., Rodrı́guez, R., & Meuth, M. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000324 · Cited by 140 · see citing works