title: Impaired removal of DNA interstrand cross-link in Nijmegen breakage syndrome and Fanconi anemia, but not in BRCA-defective group.
abstract: Human diseases characterized by a high sensitivity to DNA interstrand cross-links (ICL) and predisposition to malignance include Nijmegen breakage syndrome (NBS) and Fanconi anemia (FA), which is further classified to three groups: (1) FA core-complex group; (2) FA-ID complex group; and (3) breast cancer (BRCA)-defective group. The relationships between these four groups and the basic defect in ICL repair remain unclear. To study the details of ICL repair in NBS and FA, a highly sensitive PPB (psoralen-polyethylene oxide-biotin) dot blot assay was developed to provide sensitive quantitative measurements of ICL during the removal process. Studies utilizing this assay demonstrated a decreased rate of ICL removal in cells belonging to the FA core-complex group (e.g. groups A and G) and FA-ID complex group (group D2), while ICL removal was restored to normal levels after these cells were complemented with wt-FANCA, wt-FANCG and wt-FANCD2. Conversely, FA-D1 cells with a defective BRCA2 protein displayed normal ICL removal, although they were compromised with respect to recombination. This normal ICL removal rate in recombination-deficient cells was confirmed by using XRCC3-defective Chinese hamster cells, which are similarly compromised with respect to recombination and are sensitive to mitomycin C. The present study also showed that cells from patients with Nijmegen breakage syndrome were defective in ICL removal, while they were impaired in the recombination. These results indicate an obvious defect of FA and NBS in the ICL repair process, except in the BRCA-defective group, and a separate step of recombination-mediated repair pathway between the BRCA group and NBS.
authors.affiliation: Radiation Biology Center, Kyoto University, Yoshida-Konoecho, Kyoto, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Tsuchida
authors.forename: Kenshi
authors.initials: K
authors.lastname: Komatsu
mesh_terms: D000818:Animals; D024682:BRCA2 Protein / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D005199:Fanconi Anemia / Q000235:genetics* / Q000378:metabolism; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000378:metabolism; D006801:Humans; D051379:Mice; D049932:Nijmegen Breakage Syndrome / Q000235:genetics* / Q000378:metabolism
chemical_list: D024682:BRCA2 Protein; D052236:Fanconi Anemia Complementation Group D2 Protein; D004247:DNA
references.citation: Mutat Res. 1984 Jan;133(1):51-85
references.pmid: 6363909
references.citation: Nat Cell Biol. 2002 Dec;4(12):913-20
references.pmid: 12447395
references.citation: Lancet Oncol. 2001 Aug;2(8):483-90
references.pmid: 11905724
references.citation: Cancer Cell. 2005 Sep;8(3):255-65
references.pmid: 16153896
references.citation: Mol Cell Biol. 2001 Feb;21(3):713-20
references.pmid: 11154259
references.citation: Carcinogenesis. 1996 Dec;17(12):2597-602
references.pmid: 9006094
references.citation: Cancer Treat Res. 2002;112:109-28
references.pmid: 12481714
references.citation: Genes Dev. 2005 Dec 15;19(24):2925-40
references.pmid: 16357213
references.citation: Nat Genet. 2005 Sep;37(9):934-5
references.pmid: 16116423
references.citation: Cell. 2007 Apr 20;129(2):289-301
references.pmid: 17412408
references.citation: Nat Rev Cancer. 2003 Jan;3(1):23-34
references.pmid: 12509764
references.citation: Mol Cell. 2006 Jun 23;22(6):719-729
references.pmid: 16793542
references.citation: Nat Genet. 2007 Feb;39(2):159-61
references.pmid: 17200672
references.citation: Mol Cell Biol. 2004 Jan;24(1):123-34
references.pmid: 14673148
references.citation: J Biol Chem. 1997 Feb 7;272(6):3833-7
references.pmid: 9013642
references.citation: Blood. 2002 Oct 1;100(7):2414-20
references.pmid: 12239151
references.citation: DNA Repair (Amst). 2004 Aug-Sep;3(8-9):855-61
references.pmid: 15279770
references.citation: Mol Cell. 2001 Feb;7(2):249-62
references.pmid: 11239454
references.citation: Nucleic Acids Res. 2000 Dec 1;28(23):4800-4
references.pmid: 11095693
references.citation: Biochemistry. 1988 Aug 23;27(17):6332-8
references.pmid: 3219339
references.citation: Mol Cell Biol. 2000 Nov;20(21):7980-90
references.pmid: 11027268
references.citation: Cancer Res. 1985 Apr;45(4):1737-43
references.pmid: 3919945
references.citation: EMBO J. 2006 Oct 18;25(20):4921-32
references.pmid: 17036055
references.citation: Mol Cell Biol. 2003 Jan;23(2):754-61
references.pmid: 12509472
references.citation: Mutat Res. 1991 Sep;255(2):111-21
references.pmid: 1922147
references.citation: Mol Cell Biol. 2003 Aug;23(15):5421-30
references.pmid: 12861027
references.citation: Biochemistry. 1988 Jul 12;27(14):5174-8
references.pmid: 3167039
references.citation: DNA Repair (Amst). 2007 Nov;6(11):1670-8
references.pmid: 17669695
references.citation: Nucleic Acids Res. 2007;35(11):3733-40
references.pmid: 17517774
references.citation: Mol Cell Biol. 2004 Jul;24(13):5776-87
references.pmid: 15199134
references.citation: Mol Cell. 2003 Jul;12(1):247-54
references.pmid: 12887909
references.citation: Nature. 2002 Nov 7;420(6911):93-8
references.pmid: 12422221
references.citation: Nat Genet. 2007 Feb;39(2):162-4
references.pmid: 17200671
references.citation: Proc Natl Acad Sci U S A. 2005 Jan 25;102(4):1110-5
references.pmid: 15650050
references.citation: Cell Cycle. 2004 Feb;3(2):179-81
references.pmid: 14712086
references.citation: Mol Cell. 1998 May;1(6):783-93
references.pmid: 9660962
references.citation: Nucleic Acids Res. 1994 Aug 11;22(15):3005-10
references.pmid: 8065913
references.citation: Mutat Res. 2006 Feb 22;594(1-2):39-48
references.pmid: 16154163
references.citation: DNA Repair (Amst). 2006 May 10;5(5):566-74
references.pmid: 16569514
references.citation: Am J Hum Genet. 2007 May;80(5):895-910
references.pmid: 17436244
references.citation: Cancer Chemother Pharmacol. 1996;38(5):406-16
references.pmid: 8765433
references.citation: J Biol Chem. 2000 Aug 25;275(34):26632-6
references.pmid: 10882712
references.citation: Nucleic Acids Res. 2001 Jul 1;29(13):E66-6
references.pmid: 11433042
references.citation: Mol Cell. 2004 Aug 27;15(4):607-20
references.pmid: 15327776
references.citation: Mutat Res. 2001 Sep 4;486(4):217-47
references.pmid: 11516927
references.citation: J Biol Chem. 1998 Aug 21;273(34):21482-8
references.pmid: 9705276
references.citation: Biochemistry. 1982 Mar 2;21(5):861-71
references.pmid: 7074056