{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T22:26:34Z","timestamp":1778883994915,"version":"3.51.4"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2009,2,18]],"date-time":"2009-02-18T00:00:00Z","timestamp":1234915200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0004516","type":"journal-article","created":{"date-parts":[[2009,2,17]],"date-time":"2009-02-17T23:53:06Z","timestamp":1234914786000},"page":"e4516","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Impaired Replication Stress Response in Cells from Immunodeficiency Patients Carrying Cernunnos\/XLF Mutations"],"prefix":"10.1371","volume":"4","author":[{"given":"Michal","family":"Schwartz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifat S.","family":"Oren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Assaf C.","family":"Bester","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayelet","family":"Rahat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruthy","family":"Sfez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shlomo","family":"Yitzchaik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Pierre","family":"de Villartay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Batsheva","family":"Kerem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2009,2,18]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1146\/annurev.genet.40.110405.090451","article-title":"DNA double-strand break repair: all's well that ends well.","volume":"40","author":"C Wyman","year":"2006","journal-title":"Annu Rev Genet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1093\/carcin\/23.5.687","article-title":"Sensing and repairing DNA double-strand breaks.","volume":"23","author":"SP Jackson","year":"2002","journal-title":"Carcinogenesis"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.dnarep.2006.05.026","article-title":"Role of non-homologous end joining (NHEJ) in maintaining genomic integrity.","volume":"5","author":"S Burma","year":"2006","journal-title":"DNA Repair (Amst)"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.dnarep.2004.12.005","article-title":"Mechanism of DNA double-strand break repair by non-homologous end joining.","volume":"4","author":"ML Hefferin","year":"2005","journal-title":"DNA Repair (Amst)"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.cell.2005.12.030","article-title":"Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly.","volume":"124","author":"D Buck","year":"2006","journal-title":"Cell"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.cell.2005.12.031","article-title":"XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining.","volume":"124","author":"P Ahnesorg","year":"2006","journal-title":"Cell"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"11155","DOI":"10.1074\/jbc.M609904200","article-title":"Length-dependent binding of human XLF to DNA and stimulation of XRCC4.DNA ligase IV activity.","volume":"282","author":"H Lu","year":"2007","journal-title":"J Biol Chem"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"7851","DOI":"10.1073\/pnas.0702620104","article-title":"Cernunnos\/XLF promotes the ligation of mismatched and noncohesive DNA ends.","volume":"104","author":"CJ Tsai","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"4518","DOI":"10.1073\/pnas.0611734104","article-title":"Defective DNA repair and increased genomic instability in Cernunnos-XLF-deficient murine ES cells.","volume":"104","author":"S Zha","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1073\/pnas.0437964100","article-title":"Nonhomologous end joining and V(D)J recombination require an additional factor.","volume":"100","author":"Y Dai","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.dnarep.2006.05.022","article-title":"Differential usage of non-homologous end-joining and homologous recombination in double strand break repair.","volume":"5","author":"E Sonoda","year":"2006","journal-title":"DNA Repair (Amst)"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"3861","DOI":"10.1093\/emboj\/20.14.3861","article-title":"Characterization of homologous recombination induced by replication inhibition in mammalian cells.","volume":"20","author":"Y Saintigny","year":"2001","journal-title":"Embo J"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"5869","DOI":"10.1128\/MCB.22.16.5869-5878.2002","article-title":"Different roles for nonhomologous end joining and homologous recombination following replication arrest in mammalian cells.","volume":"22","author":"C Lundin","year":"2002","journal-title":"Mol Cell Biol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1006\/jmbi.2001.4564","article-title":"DNA double-strand breaks associated with replication forks are predominantly repaired by homologous recombination involving an exchange mechanism in mammalian cells.","volume":"307","author":"C Arnaudeau","year":"2001","journal-title":"J Mol Biol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1101\/gad.340905","article-title":"Homologous recombination and nonhomologous end-joining repair pathways regulate fragile site stability.","volume":"19","author":"M Schwartz","year":"2005","journal-title":"Genes Dev"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0168-9525(01)02303-4","article-title":"Fragile and unstable chromosomes in cancer: causes and consequences.","volume":"17","author":"RI Richards","year":"2001","journal-title":"Trends Genet"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1159\/000072843","article-title":"Common fragile sites.","volume":"100","author":"MF Arlt","year":"2003","journal-title":"Cytogenet Genome Res"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"8568","DOI":"10.1021\/bi00084a025","article-title":"DNA polymerase epsilon: aphidicolin inhibition and the relationship between polymerase and exonuclease activity.","volume":"32","author":"CH Cheng","year":"1993","journal-title":"Biochemistry"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/275458a0","article-title":"Aphidicolin prevents mitotic cell division by interfering with the activity of DNA polymerase-alpha.","volume":"275","author":"S Ikegami","year":"1978","journal-title":"Nature"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"5858","DOI":"10.1074\/jbc.273.10.5858","article-title":"DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139.","volume":"273","author":"EP Rogakou","year":"1998","journal-title":"J Biol Chem"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1083\/jcb.146.5.905","article-title":"Megabase chromatin domains involved in DNA double-strand breaks in vivo.","volume":"146","author":"EP Rogakou","year":"1999","journal-title":"J Cell Biol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"47759","DOI":"10.1074\/jbc.C100569200","article-title":"Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress.","volume":"276","author":"IM Ward","year":"2001","journal-title":"J Biol Chem"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"5057","DOI":"10.1073\/pnas.0830918100","article-title":"Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses.","volume":"100","author":"K Rothkamm","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/S1535-6108(03)00110-7","article-title":"Chk1 and Chk2 kinases in checkpoint control and cancer.","volume":"3","author":"J Bartek","year":"2003","journal-title":"Cancer Cell"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"4381","DOI":"10.1038\/sj.onc.1209466","article-title":"Depletion of CHK1, but not CHK2, induces chromosomal instability and breaks at common fragile sites.","volume":"25","author":"SG Durkin","year":"2006","journal-title":"Oncogene"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/BF00272988","article-title":"DNA polymerase alpha inhibition by aphidicolin induces gaps and breaks at common fragile sites in human chromosomes.","volume":"67","author":"TW Glover","year":"1984","journal-title":"Hum Genet"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1038\/sj.onc.1210849","article-title":"Interplay between ATM and ATR in the regulation of common fragile site stability.","volume":"27","author":"E Ozeri-Galai","year":"2008","journal-title":"Oncogene"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1083\/jcb.200705126","article-title":"Werner syndrome helicase activity is essential in maintaining fragile site stability.","volume":"180","author":"LM Pirzio","year":"2008","journal-title":"J Cell Biol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1146\/annurev.genet.41.042007.165900","article-title":"Chromosome fragile sites.","volume":"41","author":"SG Durkin","year":"2007","journal-title":"Annu Rev Genet"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1086\/422701","article-title":"Chromosomal instability at common fragile sites in seckel syndrome.","volume":"75","author":"AM Casper","year":"2004","journal-title":"Am J Hum Genet"},{"key":"ref31","article-title":"The Fanconi anemia pathway is required for the DNA replication stress response and for the regulation of common fragile site stability.","author":"NG Howlett","year":"2005","journal-title":"Hum Mol Genet"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1242\/jcs.010330","article-title":"A homologous recombination defect affects replication-fork progression in mammalian cells.","volume":"121","author":"F Daboussi","year":"2008","journal-title":"J Cell Sci"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/S0300-9084(99)00210-2","article-title":"Single molecule analysis of DNA replication.","volume":"81","author":"J Herrick","year":"1999","journal-title":"Biochimie"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0092-8674(01)00309-9","article-title":"Artemis, a novel DNA double-strand break repair\/V(D)J recombination protein, is mutated in human severe combined immune deficiency.","volume":"105","author":"D Moshous","year":"2001","journal-title":"Cell"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1172\/JCI16774","article-title":"Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis.","volume":"111","author":"D Moshous","year":"2003","journal-title":"J Clin Invest"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/S1097-2765(01)00408-7","article-title":"DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency.","volume":"8","author":"M O'Driscoll","year":"2001","journal-title":"Mol Cell"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/S0960-9822(99)80311-X","article-title":"Identification of a defect in DNA ligase IV in a radiosensitive leukaemia patient.","volume":"9","author":"E Riballo","year":"1999","journal-title":"Curr Biol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"31124","DOI":"10.1074\/jbc.M103866200","article-title":"Cellular and biochemical impact of a mutation in DNA ligase IV conferring clinical radiosensitivity.","volume":"276","author":"E Riballo","year":"2001","journal-title":"J Biol Chem"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.jmb.2007.01.018","article-title":"DNA-PK is involved in repairing a transient surge of DNA breaks induced by deceleration of DNA replication.","volume":"367","author":"T Shimura","year":"2007","journal-title":"J Mol Biol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1002\/jcp.20776","article-title":"Self-renewal of human embryonic stem cells is supported by a shortened G1 cell cycle phase.","volume":"209","author":"KA Becker","year":"2006","journal-title":"J Cell Physiol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/35006670","article-title":"DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation.","volume":"404","author":"M Difilippantonio","year":"2000","journal-title":"Nature"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/35009138","article-title":"Interplay of p53 and DNA-repair protein XRCC4 in tumorigenesis, genomic stability and development.","volume":"404","author":"Y Gao","year":"2000","journal-title":"Nature"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/S1097-2765(01)00425-7","article-title":"Impaired nonhomologous end-joining provokes soft tissue sarcomas harboring chromosomal translocations, amplifications, and deletions.","volume":"8","author":"N Sharpless","year":"2001","journal-title":"Mol Cell"},{"key":"ref44","first-page":"1107","article-title":"DNA copy number amplifications in human neoplasms: review of comparative genomic hybridization studies.","volume":"152","author":"S Knuutila","year":"1998","journal-title":"Am J Pathol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/S0002-9440(10)65166-8","article-title":"DNA copy number losses in human neoplasms.","volume":"155","author":"S Knuutila","year":"1999","journal-title":"Am J Pathol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1002\/humu.20645","article-title":"Polymorphisms of LIG4 and XRCC4 involved in the NHEJ pathway interact to modify risk of glioma.","volume":"29","author":"Y Liu","year":"2008","journal-title":"Hum Mutat"},{"key":"ref47","first-page":"2440","article-title":"Breast cancer risk associated with genotypic polymorphism of the nonhomologous end-joining genes: a multigenic study on cancer susceptibility.","volume":"63","author":"YP Fu","year":"2003","journal-title":"Cancer Res"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"5013","DOI":"10.1158\/0008-5472.CAN-04-0403","article-title":"Breast cancer risk and the DNA double-strand break end-joining capacity of nonhomologous end-joining genes are affected by BRCA1.","volume":"64","author":"DT Bau","year":"2004","journal-title":"Cancer Res"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/nature05327","article-title":"Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication.","volume":"444","author":"R Di Micco","year":"2006","journal-title":"Nature"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/nature05268","article-title":"Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints.","volume":"444","author":"J Bartkova","year":"2006","journal-title":"Nature"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1038\/nature03482","article-title":"DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis.","volume":"434","author":"J Bartkova","year":"2005","journal-title":"Nature"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/nature03485","article-title":"Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions.","volume":"434","author":"VG Gorgoulis","year":"2005","journal-title":"Nature"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"3758","DOI":"10.1073\/pnas.052545899","article-title":"DNA-dependent protein kinase suppresses double-strand break-induced and spontaneous homologous recombination.","volume":"99","author":"C Allen","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1007\/BF01790090","article-title":"Delineation of individual human chromosomes in metaphase and interphase cells by in situ suppression hybridization using recombinant DNA libraries.","volume":"80","author":"P Lichter","year":"1988","journal-title":"Hum Genet"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1126\/science.277.5331.1518","article-title":"Dynamic molecular combing: stretching the whole human genome for high-resolution studies.","volume":"277","author":"X Michalet","year":"1997","journal-title":"Science"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0004516","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T08:36:59Z","timestamp":1589013419000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0004516"}},"subtitle":[],"editor":[{"given":"Anja-Katrin","family":"Bielinsky","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2009,2,18]]},"references-count":55,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2009,2,18]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0004516","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,2,18]]}}}