{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T15:55:12Z","timestamp":1773158112402,"version":"3.50.1"},"reference-count":40,"publisher":"Proceedings of the National Academy of Sciences","issue":"10","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,5,8]]},"abstract":"<jats:p>\n            It has been suggested that delayed DNA replication underlies\n fragility at common human fragile sites, but specific sequences\n responsible for expression of these inducible fragile sites have not\n been identified. One approach to identify such cis-acting sequences\n within the large nonexonic regions of fragile sites would be to\n identify conserved functional elements within orthologous fragile sites\n by interspecies sequence comparison. This study describes a comparison\n of orthologous fragile regions, the human\n            <jats:italic>FRA3B<\/jats:italic>\n            \/\n            <jats:italic>FHIT<\/jats:italic>\n            and the murine\n            <jats:italic>Fra14A2<\/jats:italic>\n            \/\n            <jats:italic>Fhit<\/jats:italic>\n            locus. We sequenced over\n 600 kbp of the mouse\n            <jats:italic>Fra14A2<\/jats:italic>\n            , covering the region\n orthologous to the fragile epicenter of\n            <jats:italic>FRA3B<\/jats:italic>\n            , and\n determined the\n            <jats:italic>Fhit<\/jats:italic>\n            deletion break points in a mouse\n kidney cancer cell line (RENCA). The murine\n            <jats:italic>Fra14A2<\/jats:italic>\n            locus, like the human\n            <jats:italic>FRA3B<\/jats:italic>\n            , was characterized by a high\n AT content. Alignment of the two sequences showed that this fragile\n region was stable in evolution despite its susceptibility to mitotic\n recombination on inhibition of DNA replication. There were also several\n unusual highly conserved regions (HCRs). The positions of predicted\n matrix attachment regions (MARs), possibly related to replication\n origins, were not conserved. Of known fragile region landmarks, five\n cancer cell break points, one viral integration site, and one\n aphidicolin break cluster were located within or near HCRs. Thus,\n comparison of orthologous fragile regions has identified highly\n conserved sequences with possible functional roles in maintenance of\n fragility.\n          <\/jats:p>","DOI":"10.1073\/pnas.091095898","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:37:36Z","timestamp":1027694256000},"page":"5722-5727","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":55,"title":["Sequence conservation at human and mouse orthologous common fragile regions,\n            <i>FRA3B<\/i>\n            \/\n            <i>FHIT<\/i>\n            and\n            <i>Fra14A2<\/i>\n            \/\n            <i>Fhit<\/i>"],"prefix":"10.1073","volume":"98","author":[{"given":"Takeshi","family":"Shiraishi","sequence":"first","affiliation":[{"name":"Kimmel Cancer Center, Jefferson Medical College, 233 South 10th\r Street, Philadelphia, PA 19107; and Department of\r Computer Science and Engineering, Penn State University, University\r Park, PA, 16802"}]},{"given":"Teresa","family":"Druck","sequence":"additional","affiliation":[{"name":"Kimmel Cancer Center, Jefferson Medical College, 233 South 10th\r Street, Philadelphia, PA 19107; and Department of\r Computer Science and Engineering, Penn State University, University\r Park, PA, 16802"}]},{"given":"Koshi","family":"Mimori","sequence":"additional","affiliation":[{"name":"Kimmel Cancer Center, Jefferson Medical College, 233 South 10th\r Street, Philadelphia, PA 19107; and Department of\r Computer Science and Engineering, Penn State University, University\r Park, PA, 16802"}]},{"given":"Jacob","family":"Flomenberg","sequence":"additional","affiliation":[{"name":"Kimmel Cancer Center, Jefferson Medical College, 233 South 10th\r Street, Philadelphia, PA 19107; and Department of\r Computer Science and Engineering, Penn State University, University\r Park, PA, 16802"}]},{"given":"Lori","family":"Berk","sequence":"additional","affiliation":[{"name":"Kimmel Cancer Center, Jefferson Medical College, 233 South 10th\r Street, Philadelphia, PA 19107; and Department of\r Computer Science and Engineering, Penn State University, University\r Park, PA, 16802"}]},{"given":"Hansjuerg","family":"Alder","sequence":"additional","affiliation":[{"name":"Kimmel Cancer Center, Jefferson Medical College, 233 South 10th\r Street, Philadelphia, PA 19107; and Department of\r Computer Science and Engineering, Penn State University, University\r Park, PA, 16802"}]},{"given":"Webb","family":"Miller","sequence":"additional","affiliation":[{"name":"Kimmel Cancer Center, Jefferson Medical College, 233 South 10th\r Street, Philadelphia, PA 19107; and Department of\r Computer Science and Engineering, Penn State University, University\r Park, PA, 16802"}]},{"given":"Kay","family":"Huebner","sequence":"additional","affiliation":[{"name":"Kimmel Cancer Center, Jefferson Medical College, 233 South 10th\r Street, Philadelphia, PA 19107; and Department of\r Computer Science and Engineering, Penn State University, University\r Park, PA, 16802"}]},{"given":"Carlo M.","family":"Croce","sequence":"additional","affiliation":[{"name":"Kimmel Cancer Center, Jefferson Medical College, 233 South 10th\r Street, Philadelphia, PA 19107; and Department of\r Computer Science and Engineering, Penn State University, University\r Park, PA, 16802"}]}],"member":"341","published-online":{"date-parts":[[2001,4,24]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/376145a0","volume":"376","author":"Jones C","year":"1995","unstructured":"C Jones, L Penny, T Mattina, S Yu, E Baker, L Voullaire, W Y Langdon, G R Sutherland, R I Richards, A Tunnacliffe Nature (London) 376, 145\u2013149 (1995).","journal-title":"Nature (London)"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/S0092-8674(00)81875-9","volume":"88","author":"Yu S","year":"1997","unstructured":"S Yu, M Mangelsdorf, D Hewett, L Hobson, E Baker, H J Eyre, N Lapsys, D Le Paslier, N A Doggett, G R Sutherland, R I Richards Cell 88, 367\u2013374 (1997).","journal-title":"Cell"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/hmg\/5.2.187","volume":"5","author":"Wilke C M","year":"1996","unstructured":"C M Wilke, B K Hall, A Hoge, W Paradee, D I Smith, T W Glover Hum Mol Genet 5, 187\u2013195 (1996).","journal-title":"Hum Mol Genet"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"8141","DOI":"10.1073\/pnas.95.14.8141","volume":"95","author":"Mishmar D","year":"1998","unstructured":"D Mishmar, A Rahat, S W Scherer, G Nyakatura, B Hinzmann, Y Kohwi, Y Mandel-Gutfroind, J R Lee, B Drescher, D E Sas, H Margalit, M Platzer, A Weiss, L C Tsui, A Rosenthal, B Kerem Proc Natl Acad Sci USA 95, 8141\u20138146 (1998).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1002\/(SICI)1098-2264(199802)21:2<152::AID-GCC11>3.0.CO;2-T","volume":"21","author":"Huang H","year":"1998","unstructured":"H Huang, C Qian, R B Jenkins, D I Smith Genes Chromosomes Cancer 21, 152\u2013159 (1998).","journal-title":"Genes Chromosomes Cancer"},{"key":"e_1_3_4_6_2","first-page":"1683","volume":"60","author":"Mangelsdorf M","year":"2000","unstructured":"M Mangelsdorf, K Ried, E Woollatt, S Dayan, H Eyre, M Finnis, L Hobson, J Nancarrow, D Venter, E Baker, R I Richards Cancer Res 60, 1683\u20131689 (2000).","journal-title":"Cancer Res"},{"key":"e_1_3_4_7_2","first-page":"1690","volume":"60","author":"Paige A J","year":"2000","unstructured":"A J Paige, K J Taylor, A Stewart, J G Sgouros, H Gabra, G C Sellar, J F Smyth, D J Porteous, J E Watson Cancer Res 60, 1690\u20131697 (2000).","journal-title":"Cancer Res"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"14584","DOI":"10.1073\/pnas.94.26.14584","volume":"94","author":"Inoue H","year":"1997","unstructured":"H Inoue, H Ishii, H Alder, E Snyder, T Druck, K Huebner, C M Croce Proc Natl Acad Sci USA 94, 14584\u201314589 (1997).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"7456","DOI":"10.1073\/pnas.96.13.7456","volume":"96","author":"Mimori K","year":"1999","unstructured":"K Mimori, T Druck, H Inoue, H Alder, L Berk, M Mori, K Huebner, C M Croce Proc Natl Acad Sci USA 96, 7456\u20137461 (1999).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_10_2","first-page":"265","volume":"43","author":"Glover T W","year":"1988","unstructured":"T W Glover, C K Stein Am J Hum Genet 43, 265\u2013273 (1988).","journal-title":"Am J Hum Genet"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/S0092-8674(00)81034-X","volume":"84","author":"Ohta M","year":"1996","unstructured":"M Ohta, H Inoue, M G Cotticelli, K Kastury, R Baffa, J Palazzo, Z Siprashvili, M Mori, P McCue, T Druck, et al. 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