The ATR barrier to replication-born DNA damage

Jackson, 2009, The DNA-damage response in human biology and disease, Nature, 461, 1071, 10.1038/nature08467

Savitsky, 1995, A single ataxia telangiectasia gene with a product similar to PI-3 kinase, Science, 268, 1749, 10.1126/science.7792600

Harper, 2007, The DNA damage response: ten years after, Mol. Cell., 28, 739, 10.1016/j.molcel.2007.11.015

Cimprich, 2008, ATR: an essential regulator of genome integrity, Nat. Rev. Mol. Cell. Biol., 9, 616, 10.1038/nrm2450

Shiloh, 2003, ATM and related protein kinases: safeguarding genome integrity, Nat. Rev. Cancer, 3, 155, 10.1038/nrc1011

Meek, 2008, DNA-PK: the means to justify the ends?, Adv. Immunol., 99, 33, 10.1016/S0065-2776(08)00602-0

Stiff, 2004, ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation, Cancer Res., 64, 2390, 10.1158/0008-5472.CAN-03-3207

Gurley, 2001, Synthetic lethality between mutation in ATM and DNAPK(cs) during murine embryogenesis, Curr. Biol., 11, 191, 10.1016/S0960-9822(01)00048-3

Lavin, 2008, Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer, Nat. Rev. Mol. Cell. Biol., 9, 759, 10.1038/nrm2514

Mordes, 2008, TopBP1 activates ATR through ATRIP and a PIKK regulatory domain, Genes Dev., 22, 1478, 10.1101/gad.1666208

Matsuoka, 2007, ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage, Science, 316, 1160, 10.1126/science.1140321

Cuadrado, 2006, ATM regulates ATR chromatin loading in response to DNA double-strand breaks, J. Exp. Med., 203, 297, 10.1084/jem.20051923

Jazayeri, 2006, ATM-and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks, Nat. Cell Biol., 8, 37, 10.1038/ncb1337

Toledo, 2008, ATR signaling can drive cells into senescence in the absence of DNA breaks, Genes Dev., 22, 297, 10.1101/gad.452308

Kumagai, 2000, a novel protein required for the activation of Chk1 during a DNA replication checkpoint response in Xenopus egg extracts, Mol. Cell, 6, 839, 10.1016/S1097-2765(05)00092-4

Paull, 1998, The 3′ to 5′ exonuclease activity of Mre 11 facilitates repair of DNA double-strand breaks, Mol. Cell, 1, 969, 10.1016/S1097-2765(00)80097-0

Nimonkar, 2008, Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair, Proc. Natl. Acad. Sci. U. S. A., 105, 16906, 10.1073/pnas.0809380105

Sartori, 2007, Human CtIP promotes DNA end resection, Nature, 450, 509, 10.1038/nature06337

Zou, 2003, Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes, Science, 300, 1542, 10.1126/science.1083430

Garvik, 1995, Single-stranded DNA arising at telomeres in cdc13 mutants may constitute a specific signal for the RAD9 checkpoint, Mol Cell Biol., 15, 6128, 10.1128/MCB.15.11.6128

Lee, 1998, Saccharomyces Ku70, mre11/rad50 and RPA proteins regulate adaptation to G2/M arrest after DNA damage, Cell, 94, 399, 10.1016/S0092-8674(00)81482-8

Cortez, 2001, ATR and ATRIP: partners in checkpoint signaling, Science, 294, 1713, 10.1126/science.1065521

Byun, 2005, Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint, Genes Dev., 19, 1040, 10.1101/gad.1301205

Halazonetis, 2008, An oncogene-induced DNA damage model for cancer development, Science, 319, 1352, 10.1126/science.1140735

Branzei, 2010, Maintaining genome stability at the replication fork, Nat. Rev. Mol. Cell. Biol., 11, 208, 10.1038/nrm2852

Yang, 2006, Recruitment of ATR–ATRIP, Rad17, and 9-1-1 complexes to DNA damage, Methods Enzymol., 409, 118, 10.1016/S0076-6879(05)09007-5

Lee, 2007, The Rad9-Hus1-Rad1 checkpoint clamp regulates interaction of TopBP1 with ATR, J. Biol. Chem., 282, 28036, 10.1074/jbc.M704635200

Cimprich, 1996, cDNA cloning and gene mapping of a candidate human cell cycle checkpoint protein, Proc. Natl. Acad. Sci. U. S. A., 93, 2850, 10.1073/pnas.93.7.2850

Liu, 2000, Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint, Genes Dev., 14, 1448, 10.1101/gad.14.12.1448

Huertas, 2009, Human CtIP mediates cell cycle control of DNA end resection and double strand break repair, J. Biol. Chem., 284, 9558, 10.1074/jbc.M808906200

Hirao, 2002, Chk2 is a tumor suppressor that regulates apoptosis in both an ataxia telangiectasia mutated (ATM)-dependent and an ATM-independent manner, Mol Cell Biol., 22, 6521, 10.1128/MCB.22.18.6521-6532.2002

Takai, 2002, Chk2-deficient mice exhibit radioresistance and defective p53-mediated transcription, EMBO J., 21, 5195, 10.1093/emboj/cdf506

Fernandez-Capetillo, 2002, DNA damage-induced G2-M checkpoint activation by histone H2AX and 53BP1, Nat. Cell Biol., 4, 993, 10.1038/ncb884

Smits, 2006, Rapid PIKK-dependent release of Chk1 from chromatin promotes the DNA-damage checkpoint response, Curr. Biol., 16, 150, 10.1016/j.cub.2005.11.066

Bartek, 2003, Chk1 and Chk2 kinases in checkpoint control and cancer, Cancer Cell, 3, 421, 10.1016/S1535-6108(03)00110-7

Jin, 2003, SCFbeta-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase, Genes Dev., 17, 3062, 10.1101/gad.1157503

Xiao, 2003, Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents, J. Biol. Chem., 278, 21767, 10.1074/jbc.M300229200

Syljuasen, 2005, Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage, Mol Cell Biol., 25, 3553, 10.1128/MCB.25.9.3553-3562.2005

Beck, 2010, Regulators of cyclin-dependent kinases are crucial for maintaining genome integrity in S phase, J. Cell Biol., 188, 629, 10.1083/jcb.200905059

Melixetian, 2009, NEK11 regulates CDC25A degradation and the IR-induced G2/M checkpoint, Nat. Cell Biol., 11, 1247, 10.1038/ncb1969

Taylor, 2001, Regulation of the G2/M transition by p53, Oncogene, 20, 1803, 10.1038/sj.onc.1204252

Bartkova, 2006, Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints, Nature, 444, 633, 10.1038/nature05268

Di Micco, 2006, Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication, Nature, 444, 638, 10.1038/nature05327

Mallette, 2007, The DNA damage signaling pathway is a critical mediator of oncogene-induced senescence, Genes Dev., 21, 43, 10.1101/gad.1487307

Tercero, 2001, Regulation of DNA replication fork progression through damaged DNA by the Mec1/Rad53 checkpoint, Nature, 412, 553, 10.1038/35087607

Hanada, 2007, The structure-specific endonuclease Mus81 contributes to replication restart by generating double-strand DNA breaks, Nat. Struct. Mol. Biol., 14, 1096, 10.1038/nsmb1313

Friedel, 2009, ATR/Mec1: coordinating fork stability and repair, Curr. Opin. Cell Biol., 21, 237, 10.1016/j.ceb.2009.01.017

Brown, 2000, ATR disruption leads to chromosomal fragmentation and early embryonic lethality, Genes Dev., 14, 397, 10.1101/gad.14.4.397

de Klein, 2000, Targeted disruption of the cell-cycle checkpoint gene ATR leads to early embryonic lethality in mice, Curr. Biol., 10, 479, 10.1016/S0960-9822(00)00447-4

Takai, 2000, Aberrant cell cycle checkpoint function and early embryonic death in Chk1(−/−) mice, Genes Dev., 14, 1439, 10.1101/gad.14.12.1439

O’Driscoll, 2003, A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome, Nat. Genet., 33, 497, 10.1038/ng1129

Murga, 2009, A mouse model of ATR-Seckel shows embryonic replicative stress and accelerated aging, Nat. Genet., 41, 891, 10.1038/ng.420

Cobb, 2003, DNA polymerase stabilization at stalled replication forks requires Mec1 and the RecQ helicase Sgs1, EMBO J., 22, 4325, 10.1093/emboj/cdg391

Lou, 2008, Mrc1 and DNA polymerase epsilon function together in linking DNA replication and the S phase checkpoint, Mol. Cell, 32, 106, 10.1016/j.molcel.2008.08.020

Davies, 2007, Role for BLM in replication-fork restart and suppression of origin firing after replicative stress, Nat. Struct. Mol. Biol., 14, 677, 10.1038/nsmb1267

Pirzio, 2008, Werner syndrome helicase activity is essential in maintaining fragile site stability, J. Cell Biol., 180, 305, 10.1083/jcb.200705126

Ge, 2007, Dormant origins licensed by excess Mcm2-7 are required for human cells to survive replicative stress, Genes Dev., 21, 3331, 10.1101/gad.457807

Shechter, 2004, ATR and ATM regulate the timing of DNA replication origin firing, Nat. Cell Biol., 6, 648, 10.1038/ncb1145

Wang, 2004, ATR affecting cell radiosensitivity is dependent on homologous recombination repair but independent of nonhomologous end joining, Cancer Res., 64, 7139, 10.1158/0008-5472.CAN-04-1289

Foray, 2003, A subset of ATM- and ATR-dependent phosphorylation events requires the BRCA1 protein, EMBO J., 22, 2860, 10.1093/emboj/cdg274

Tibbetts, 2000, Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress, Genes Dev., 14, 2989, 10.1101/gad.851000

Turner, 2004, BRCA1, histone H2AX phosphorylation, and male meiotic sex chromosome inactivation, Curr. Biol., 14, 2135, 10.1016/j.cub.2004.11.032

Sorensen, 2005, The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair, Nat. Cell Biol., 7, 195, 10.1038/ncb1212

Andreassen, 2004, ATR couples FANCD2 monoubiquitination to the DNA-damage response, Genes Dev., 18, 1958, 10.1101/gad.1196104

Collis, 2008, FANCM, FAAP24 function in ATR-mediated checkpoint signaling independently of the Fanconi anemia core complex, Mol. Cell, 32, 313, 10.1016/j.molcel.2008.10.014

O’Driscoll, 2009, Mouse models for ATR deficiency, DNA Repair (Amst.), 8, 1333, 10.1016/j.dnarep.2009.09.001

Bartkova, 2005, DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis, Nature, 434, 864, 10.1038/nature03482

Gorgoulis, 2005, Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions, Nature, 434, 907, 10.1038/nature03485

Pusapati, 2006, ATM promotes apoptosis and suppresses tumorigenesis in response to Myc, Proc. Natl. Acad. Sci. U. S. A., 103, 1446, 10.1073/pnas.0507367103

Efeyan, 2009, Limited role of murine ATM in oncogene-induced senescence and p53-dependent tumor suppression, PLoS One, 4, e5475, 10.1371/journal.pone.0005475

Fang, 2004, ATR functions as a gene dosage-dependent tumor suppressor on a mismatch repair-deficient background, EMBO J., 23, 3164, 10.1038/sj.emboj.7600315

Lam, 2004, Chk1 is haploinsufficient for multiple functions critical to tumor suppression, Cancer Cell, 6, 45, 10.1016/j.ccr.2004.06.015

Tao, 2006, Chk1 inhibitors for novel cancer treatment, Anticancer Agents Med. Chem., 6, 377, 10.2174/187152006777698132

Koniaras, 2001, Inhibition of Chk1-dependent G2 DNA damage checkpoint radiosensitizes p53 mutant human cells, Oncogene, 20, 7453, 10.1038/sj.onc.1204942

Ruzankina, 2009, Tissue regenerative delays and synthetic lethality in adult mice after combined deletion of Atr and Trp53, Nat. Genet., 41, 1144, 10.1038/ng.441

Heffernan, 2009, 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., 129, 1805, 10.1038/jid.2008.435

Garinis, 2008, DNA damage and ageing: new-age ideas for an age-old problem, Nat. Cell Biol., 10, 1241, 10.1038/ncb1108-1241

Rossi, 2007, Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age, Nature, 447, 725, 10.1038/nature05862

Sedelnikova, 2004, Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks, Nat. Cell Biol., 6, 168, 10.1038/ncb1095

Ruzankina, 2007, Deletion of the developmentally essential gene ATR in adult mice leads to age-related phenotypes and stem cell loss, Cell Stem Cell, 1, 113, 10.1016/j.stem.2007.03.002

Fernandez-Capetillo, 2010, Intrauterine programming of ageing, EMBO Rep., 11, 32, 10.1038/embor.2009.262