{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:52:55Z","timestamp":1789707175723,"version":"4.0.1"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2013,10,24]],"date-time":"2013-10-24T00:00:00Z","timestamp":1382572800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"DOI":"10.1038\/ncomms3578","type":"journal-article","created":{"date-parts":[[2013,10,24]],"date-time":"2013-10-24T10:19:46Z","timestamp":1382609986000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Heterozygous mutations in PALB2 cause DNA replication and damage response defects"],"prefix":"10.1038","volume":"4","author":[{"given":"Jenni","family":"Nikkil\u00e4","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Christin Parplys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katri","family":"Pylk\u00e4s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muthiah","family":"Bose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanying","family":"Huo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Borgmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Rapakko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pentti","family":"Nieminen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"Pospiech","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Winqvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,10,24]]},"reference":[{"key":"BFncomms3578_CR1","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1016\/j.molcel.2006.05.022","volume":"22","author":"B Xia","year":"2006","unstructured":"Xia, B. et al. Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Mol. Cell 22, 719\u2013729 (2006).","journal-title":"Mol. Cell"},{"key":"BFncomms3578_CR2","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.cub.2009.02.018","volume":"19","author":"F Zhang","year":"2009","unstructured":"Zhang, F. et al. PALB2 links BRCA1 and BRCA2 in the DNA-damage response. Curr. Biol. 19, 524\u2013529 (2009).","journal-title":"Curr. Biol."},{"key":"BFncomms3578_CR3","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1038\/nsmb.1916","volume":"17","author":"E Dray","year":"2010","unstructured":"Dray, E. et al. Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2. Nat. Struct. Mol. Biol. 17, 1255\u20131259 (2010).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"BFncomms3578_CR4","doi-asserted-by":"publisher","first-page":"7353","DOI":"10.1158\/0008-5472.CAN-10-1012","volume":"70","author":"M Tischkowitz","year":"2010","unstructured":"Tischkowitz, M. & Xia, B. PALB2\/FANCN\u2014recombining cancer and Fanconi anemia. Cancer Res. 70, 7353\u20137359 (2010).","journal-title":"Cancer Res."},{"key":"BFncomms3578_CR5","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/ng1942","volume":"39","author":"B Xia","year":"2007","unstructured":"Xia, B. et al. Fanconi anemia is associated with a defect in the BRCA2 partner PALB2. Nat. Genet. 39, 159\u2013161 (2007).","journal-title":"Nat. Genet."},{"key":"BFncomms3578_CR6","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/nature05609","volume":"446","author":"H Erkko","year":"2007","unstructured":"Erkko, H. et al. A recurrent mutation in PALB2 in Finnish cancer families. Nature 446, 316\u2013319 (2007).","journal-title":"Nature"},{"key":"BFncomms3578_CR7","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/ng1959","volume":"39","author":"N Rahman","year":"2007","unstructured":"Rahman, N. et al. PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat. Genet. 39, 165\u2013167 (2007).","journal-title":"Nat. Genet."},{"key":"BFncomms3578_CR8","doi-asserted-by":"publisher","first-page":"R109","DOI":"10.1186\/bcr2796","volume":"12","author":"MC Southey","year":"2010","unstructured":"Southey, M. C. et al. A PALB2 mutation associated with high risk of breast cancer. Breast Cancer Res. 12, R109 (2010).","journal-title":"Breast Cancer Res."},{"key":"BFncomms3578_CR9","doi-asserted-by":"publisher","first-page":"4667","DOI":"10.1158\/1078-0432.CCR-08-0210","volume":"14","author":"H Erkko","year":"2008","unstructured":"Erkko, H. et al. Penetrance analysis of the PALB2 c.1592delT founder mutation. Clin. Cancer Res. 14, 4667\u20134671 (2008).","journal-title":"Clin. Cancer Res."},{"key":"BFncomms3578_CR10","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1038\/ng1947","volume":"39","author":"S Reid","year":"2007","unstructured":"Reid, S. et al. Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. Nat. Genet. 39, 162\u2013164 (2007).","journal-title":"Nat. Genet."},{"key":"BFncomms3578_CR11","doi-asserted-by":"publisher","first-page":"E2176","DOI":"10.1002\/humu.21478","volume":"32","author":"H Hellebrand","year":"2011","unstructured":"Hellebrand, H. et al. Germline mutations in the PALB2 gene are population specific and occur with low frequencies in familial breast cancer. Hum. Mutat. 32, E2176\u2013E2188 (2011).","journal-title":"Hum. Mutat."},{"key":"BFncomms3578_CR12","doi-asserted-by":"publisher","first-page":"2222","DOI":"10.1158\/0008-5472.CAN-10-3958","volume":"71","author":"S Casadei","year":"2011","unstructured":"Casadei, S. et al. Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer. Cancer Res. 71, 2222\u20132229 (2011).","journal-title":"Cancer Res."},{"key":"BFncomms3578_CR13","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1002\/humu.22022","volume":"33","author":"M Tischkowitz","year":"2012","unstructured":"Tischkowitz, M. et al. Rare germline mutations in PALB2 and breast cancer risk: a population-based study. Hum. Mutat. 33, 674\u2013680 (2012).","journal-title":"Hum. Mutat."},{"key":"BFncomms3578_CR14","doi-asserted-by":"publisher","first-page":"2601","DOI":"10.1038\/emboj.2009.206","volume":"28","author":"HE Bryant","year":"2009","unstructured":"Bryant, H. E. et al. PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination. EMBO J. 28, 2601\u20132615 (2009).","journal-title":"EMBO J."},{"key":"BFncomms3578_CR15","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1038\/emboj.2009.385","volume":"29","author":"RA Schwab","year":"2010","unstructured":"Schwab, R. A. et al. ATR activation and replication fork restart are defective in FANCM-deficient cells. EMBO J. 29, 806\u2013818 (2010).","journal-title":"EMBO J."},{"key":"BFncomms3578_CR16","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1242\/jcs.010330","volume":"121","author":"F Daboussi","year":"2008","unstructured":"Daboussi, F. et al. A homologous recombination defect affects replication-fork progression in mammalian cells. J. Cell Sci. 121, 162\u2013166 (2008).","journal-title":"J. Cell Sci."},{"key":"BFncomms3578_CR17","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1101\/gad.2029711","volume":"25","author":"N Karnani","year":"2011","unstructured":"Karnani, N. & Dutta, A. The effect of the intra-S-phase checkpoint on origins of replication in human cells. Genes Dev. 25, 621\u2013633 (2011).","journal-title":"Genes Dev."},{"key":"BFncomms3578_CR18","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1101\/gad.840500","volume":"14","author":"Q Liu","year":"2000","unstructured":"Liu, Q. et al. Chk1 is an essential kinase that is regulated by Atr and required for the G(2)\/M DNA damage checkpoint. Genes Dev. 14, 1448\u20131459 (2000).","journal-title":"Genes Dev."},{"key":"BFncomms3578_CR19","doi-asserted-by":"publisher","first-page":"4129","DOI":"10.1128\/MCB.21.13.4129-4139.2001","volume":"21","author":"H Zhao","year":"2001","unstructured":"Zhao, H. & Piwnica-Worms, H. ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1. Mol. Cell Biol. 21, 4129\u20134139 (2001).","journal-title":"Mol. Cell Biol."},{"key":"BFncomms3578_CR20","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1083\/jcb.201007074","volume":"191","author":"XQ Ge","year":"2010","unstructured":"Ge, X. Q. & Blow, J. J. Chk1 inhibits replication factory activation but allows dormant origin firing in existing factories. J. Cell Biol. 191, 1285\u20131297 (2010).","journal-title":"J. Cell Biol."},{"key":"BFncomms3578_CR21","doi-asserted-by":"publisher","first-page":"3553","DOI":"10.1128\/MCB.25.9.3553-3562.2005","volume":"25","author":"RG Syljuasen","year":"2005","unstructured":"Syljuasen, R. G. et al. Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage. Mol. Cell. Biol 25, 3553\u20133562 (2005).","journal-title":"Mol. Cell. Biol"},{"key":"BFncomms3578_CR22","doi-asserted-by":"publisher","first-page":"2203","DOI":"10.4161\/cc.5.19.3256","volume":"5","author":"E Petermann","year":"2006","unstructured":"Petermann, E. & Caldecott, K. W. Evidence that the ATR\/Chk1 pathway maintains normal replication fork progression during unperturbed S phase. Cell Cycle 5, 2203\u20132209 (2006).","journal-title":"Cell Cycle"},{"key":"BFncomms3578_CR23","doi-asserted-by":"publisher","first-page":"2719","DOI":"10.1038\/sj.emboj.7601714","volume":"26","author":"A Maya-Mendoza","year":"2007","unstructured":"Maya-Mendoza, A., Petermann, E., Gillespie, D. A., Caldecott, K. W. & Jackson, D. A. Chk1 regulates the density of active replication origins during the vertebrate S phase. EMBO J. 26, 2719\u20132731 (2007).","journal-title":"EMBO J."},{"key":"BFncomms3578_CR24","doi-asserted-by":"publisher","first-page":"16090","DOI":"10.1073\/pnas.1005031107","volume":"107","author":"E Petermann","year":"2010","unstructured":"Petermann, E., Woodcock, M. & Helleday, T. Chk1 promotes replication fork progression by controlling replication initiation. Proc. Natl Acad. Sci. USA 107, 16090\u201316095 (2010).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms3578_CR25","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1016\/j.ceb.2010.07.015","volume":"22","author":"H Araki","year":"2010","unstructured":"Araki, H. Cyclin-dependent kinase-dependent initiation of chromosomal DNA replication. Curr. Opin. Cell Biol. 22, 766\u2013771 (2010).","journal-title":"Curr. Opin. Cell Biol."},{"key":"BFncomms3578_CR26","doi-asserted-by":"publisher","first-page":"4226","DOI":"10.1128\/MCB.00412-12","volume":"32","author":"H Beck","year":"2012","unstructured":"Beck, H. et al. Cyclin-dependent kinase suppression by WEE1 kinase protects the genome through control of replication initiation and nucleotide consumption. Mol. Cell Biol. 32, 4226\u20134236 (2012).","journal-title":"Mol. Cell Biol."},{"key":"BFncomms3578_CR27","doi-asserted-by":"publisher","first-page":"9693","DOI":"10.1158\/0008-5472.CAN-10-2286","volume":"70","author":"O Gilad","year":"2010","unstructured":"Gilad, O. et al. Combining ATR suppression with oncogenic Ras synergistically increases genomic instability, causing synthetic lethality or tumorigenesis in a dosage-dependent manner. Cancer Res. 70, 9693\u20139702 (2010).","journal-title":"Cancer Res."},{"key":"BFncomms3578_CR28","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1101\/gad.1067403","volume":"17","author":"EJ Brown","year":"2003","unstructured":"Brown, E. J. & Baltimore, D. Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance. Genes Dev. 17, 615\u2013628 (2003).","journal-title":"Genes Dev."},{"key":"BFncomms3578_CR29","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1038\/embor.2011.99","volume":"12","author":"T Menzel","year":"2011","unstructured":"Menzel, T. et al. A genetic screen identifies BRCA2 and PALB2 as key regulators of G2 checkpoint maintenance. EMBO Rep. 12, 705\u2013712 (2011).","journal-title":"EMBO Rep."},{"key":"BFncomms3578_CR30","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/S0076-6879(05)09015-4","volume":"409","author":"JW Theunissen","year":"2006","unstructured":"Theunissen, J. W. & Petrini, J. H. Methods for studying the cellular response to DNA damage: influence of the Mre11 complex on chromosome metabolism. Methods Enzymol. 409, 251\u2013284 (2006).","journal-title":"Methods Enzymol."},{"key":"BFncomms3578_CR31","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.ceb.2009.01.018","volume":"21","author":"HC Reinhardt","year":"2009","unstructured":"Reinhardt, H. C. & Yaffe, M. B. Kinases that control the cell cycle in response to DNA damage: Chk1, Chk2, and MK2. Curr. Opin. Cell Biol. 21, 245\u2013255 (2009).","journal-title":"Curr. Opin. Cell Biol."},{"key":"BFncomms3578_CR32","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/978-0-387-70630-6_14","volume":"597","author":"V Soni","year":"2007","unstructured":"Soni, V., Cahir-McFarland, E. & Kieff, E. LMP1 TRAFficking activates growth and survival pathways. Adv. Exp. Med. Biol. 597, 173\u2013187 (2007).","journal-title":"Adv. Exp. Med. Biol."},{"key":"BFncomms3578_CR33","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","volume":"144","author":"D Hanahan","year":"2011","unstructured":"Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646\u2013674 (2011).","journal-title":"Cell"},{"key":"BFncomms3578_CR34","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1126\/science.1140735","volume":"319","author":"TD Halazonetis","year":"2008","unstructured":"Halazonetis, T. D., Gorgoulis, V. G. & Bartek, J. An oncogene-induced DNA damage model for cancer development. Science 319, 1352\u20131355 (2008).","journal-title":"Science"},{"key":"BFncomms3578_CR35","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/nature03485","volume":"434","author":"VG Gorgoulis","year":"2005","unstructured":"Gorgoulis, V. G. et al. Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 434, 907\u2013913 (2005).","journal-title":"Nature"},{"key":"BFncomms3578_CR36","doi-asserted-by":"publisher","first-page":"17773","DOI":"10.1073\/pnas.1110969108","volume":"108","author":"H Konishi","year":"2011","unstructured":"Konishi, H. et al. Mutation of a single allele of the cancer susceptibility gene BRCA1 leads to genomic instability in human breast epithelial cells. Proc. Natl Acad. Sci. USA 108, 17773\u201317778 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms3578_CR37","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1093\/carcin\/bgi360","volume":"27","author":"K Heikkinen","year":"2006","unstructured":"Heikkinen, K. et al. RAD50 and NBS1 are breast cancer susceptibility genes associated with genomic instability. Carcinogenesis 27, 1593\u20131599 (2006).","journal-title":"Carcinogenesis"},{"key":"BFncomms3578_CR38","unstructured":"Verma R. S., Babu A. (ed.)Human chromosomes, manual of basic techniques Pergamon Press, Inc (1989)."},{"key":"BFncomms3578_CR39","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/j.radonc.2012.01.005","volume":"102","author":"AC Parplys","year":"2012","unstructured":"Parplys, A. C., Petermann, E., Petersen, C., Dikomey, E. & Borgmann, K. DNA damage by X-rays and their impact on replication processes. Radiother. Oncol. 102, 466\u2013471 (2012).","journal-title":"Radiother. Oncol."},{"key":"BFncomms3578_CR40","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1083\/jcb.140.6.1285","volume":"140","author":"DA Jackson","year":"1998","unstructured":"Jackson, D. A. & Pombo, A. Replicon clusters are stable units of chromosome structure: evidence that nuclear organization contributes to the efficient activation and propagation of S phase in human cells. J. Cell Biol. 140, 1285\u20131295 (1998).","journal-title":"J. Cell Biol."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/ncomms3578.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ncomms3578","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms3578.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T01:19:37Z","timestamp":1672967977000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncomms3578"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,24]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2013,12,20]]}},"alternative-id":["BFncomms3578"],"URL":"https:\/\/doi.org\/10.1038\/ncomms3578","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,24]]},"assertion":[{"value":"6 November 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 September 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 October 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2578"}}