PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
 
Mol Cell Biol. 1997 December; 17(12): 6822–6830.
PMCID: PMC232538

Initiation of DNA interstrand cross-link repair in humans: the nucleotide excision repair system makes dual incisions 5' to the cross-linked base and removes a 22- to 28-nucleotide-long damage-free strand.

Abstract

Most DNA repair mechanisms rely on the redundant information inherent to the duplex to remove damaged nucleotides and replace them with normal ones, using the complementary strand as a template. Interstrand cross-links pose a unique challenge to the DNA repair machinery because both strands are damaged. To study the repair of interstrand cross-links by mammalian cells, we tested the activities of cell extracts of wild-type or excision repair-defective rodent cell lines and of purified human excision nuclease on a duplex with a site-specific cross-link. We found that in contrast to monoadducts, which are removed by dual incisions bracketing the lesion, the cross-link causes dual incisions, both 5' to the cross-link in one of the two strands. The net result is the generation of a 22- to 28-nucleotide-long gap immediately 5' to the cross-link. This gap may act as a recombinogenic signal to initiate cross-link removal.

Full Text

The Full Text of this article is available as a PDF (789K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bardwell AJ, Bardwell L, Tomkinson AE, Friedberg EC. Specific cleavage of model recombination and repair intermediates by the yeast Rad1-Rad10 DNA endonuclease. Science. 1994 Sep 30;265(5181):2082–2085. [PubMed]
  • Bessho T, Sancar A, Thompson LH, Thelen MP. Reconstitution of human excision nuclease with recombinant XPF-ERCC1 complex. J Biol Chem. 1997 Feb 7;272(6):3833–3837. [PubMed]
  • Bredberg A, Söderhäll S. Normal rate of DNA breakage in xeroderma pigmentosum complementation group E cells treated with 8-methoxypsoralen plus near-ultraviolet radiation. Biochim Biophys Acta. 1985 Mar 20;824(3):268–271. [PubMed]
  • Calsou P, Sage E, Moustacchi E, Salles B. Preferential repair incision of cross-links versus monoadducts in psoralen-damaged plasmid DNA by human cell-free extracts. Biochemistry. 1996 Nov 26;35(47):14963–14969. [PubMed]
  • Chatterjee PK, Cantor CR. Photochemical production of psoralen - DNA monoadducts capable of subsequent photocrosslinking. Nucleic Acids Res. 1978 Oct;5(10):3619–3633. [PMC free article] [PubMed]
  • Cheng S, Sancar A, Hearst JE. RecA-dependent incision of psoralen-crosslinked DNA by (A)BC excinuclease. Nucleic Acids Res. 1991 Feb 11;19(3):657–663. [PMC free article] [PubMed]
  • Cheng S, Van Houten B, Gamper HB, Sancar A, Hearst JE. Use of psoralen-modified oligonucleotides to trap three-stranded RecA-DNA complexes and repair of these cross-linked complexes by ABC excinuclease. J Biol Chem. 1988 Oct 15;263(29):15110–15117. [PubMed]
  • Cimino GD, Gamper HB, Isaacs ST, Hearst JE. Psoralens as photoactive probes of nucleic acid structure and function: organic chemistry, photochemistry, and biochemistry. Annu Rev Biochem. 1985;54:1151–1193. [PubMed]
  • Cole RS. Repair of DNA containing interstrand crosslinks in Escherichia coli: sequential excision and recombination. Proc Natl Acad Sci U S A. 1973 Apr;70(4):1064–1068. [PubMed]
  • Dardalhon M, Averbeck D. Pulsed-field gel electrophoresis analysis of the repair of psoralen plus UVA induced DNA photoadducts in Saccharomyces cerevisiae. Mutat Res. 1995 Jan;336(1):49–60. [PubMed]
  • Digweed M, Sperling K. Molecular analysis of Fanconi anaemia. Bioessays. 1996 Jul;18(7):579–585. [PubMed]
  • Evans E, Fellows J, Coffer A, Wood RD. Open complex formation around a lesion during nucleotide excision repair provides a structure for cleavage by human XPG protein. EMBO J. 1997 Feb 3;16(3):625–638. [PubMed]
  • Faruqi AF, Seidman MM, Segal DJ, Carroll D, Glazer PM. Recombination induced by triple-helix-targeted DNA damage in mammalian cells. Mol Cell Biol. 1996 Dec;16(12):6820–6828. [PMC free article] [PubMed]
  • Fishman-Lobell J, Haber JE. Removal of nonhomologous DNA ends in double-strand break recombination: the role of the yeast ultraviolet repair gene RAD1. Science. 1992 Oct 16;258(5081):480–484. [PubMed]
  • Fornace AJ, Jr, Little JB, Weichselbaum RR. DNA repair in a Fanconi's anemia fibroblast cell strain. Biochim Biophys Acta. 1979 Jan 26;561(1):99–109. [PubMed]
  • Fujiwara Y, Tatsumi M. Cross-link repair in human cells and its possible defect in Fanconi's anemia cells. J Mol Biol. 1977 Jul 15;113(4):635–649. [PubMed]
  • Fujiwara Y, Nakamura M, Yokoo S. A new anticancer platinum compound, (-)-(R)-2-aminomethyl-pyrrolidine(1,1-cyclobutanedicarboxylato) platinum(II): DNA interstrand crosslinking, repair and lethal effects in normal human, Fanconi's anaemia and xeroderma pigmentosum cells. Br J Cancer. 1993 Jun;67(6):1285–1292. [PMC free article] [PubMed]
  • Hoy CA, Thompson LH, Mooney CL, Salazar EP. Defective DNA cross-link removal in Chinese hamster cell mutants hypersensitive to bifunctional alkylating agents. Cancer Res. 1985 Apr;45(4):1737–1743. [PubMed]
  • Huang JC, Svoboda DL, Reardon JT, Sancar A. Human nucleotide excision nuclease removes thymine dimers from DNA by incising the 22nd phosphodiester bond 5' and the 6th phosphodiester bond 3' to the photodimer. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3664–3668. [PubMed]
  • Huang JC, Hsu DS, Kazantsev A, Sancar A. Substrate spectrum of human excinuclease: repair of abasic sites, methylated bases, mismatches, and bulky adducts. Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12213–12217. [PubMed]
  • Huang JC, Sancar A. Determination of minimum substrate size for human excinuclease. J Biol Chem. 1994 Jul 22;269(29):19034–19040. [PubMed]
  • Islas AL, Vos JM, Hanawalt PC. Differential introduction and repair of psoralen photoadducts to DNA in specific human genes. Cancer Res. 1991 Jun 1;51(11):2867–2873. [PubMed]
  • Ivanov EL, Haber JE. RAD1 and RAD10, but not other excision repair genes, are required for double-strand break-induced recombination in Saccharomyces cerevisiae. Mol Cell Biol. 1995 Apr;15(4):2245–2251. [PMC free article] [PubMed]
  • Jachymczyk WJ, von Borstel RC, Mowat MR, Hastings PJ. Repair of interstrand cross-links in DNA of Saccharomyces cerevisiae requires two systems for DNA repair: the RAD3 system and the RAD51 system. Mol Gen Genet. 1981;182(2):196–205. [PubMed]
  • Jeggo PA, Taccioli GE, Jackson SP. Menage à trois: double strand break repair, V(D)J recombination and DNA-PK. Bioessays. 1995 Nov;17(11):949–957. [PubMed]
  • Jones BK, Yeung AT. DNA base composition determines the specificity of UvrABC endonuclease incision of a psoralen cross-link. J Biol Chem. 1990 Feb 25;265(6):3489–3496. [PubMed]
  • Jones NJ. Genetic analysis of mitomycin C-hypersensitive Chinese hamster cell mutants. Mutagenesis. 1994 Sep;9(5):477–482. [PubMed]
  • Kaye J, Smith CA, Hanawalt PC. DNA repair in human cells containing photoadducts of 8-methoxypsoralen or angelicin. Cancer Res. 1980 Mar;40(3):696–702. [PubMed]
  • Kohn KW. Beyond DNA cross-linking: history and prospects of DNA-targeted cancer treatment--fifteenth Bruce F. Cain Memorial Award Lecture. Cancer Res. 1996 Dec 15;56(24):5533–5546. [PubMed]
  • Kumaresan KR, Hang B, Lambert MW. Human endonucleolytic incision of DNA 3' and 5' to a site-directed psoralen monoadduct and interstrand cross-link. J Biol Chem. 1995 Dec 22;270(51):30709–30716. [PubMed]
  • Magaña-Schwencke N, Henriques JA, Chanet R, Moustacchi E. The fate of 8-methoxypsoralen photoinduced crosslinks in nuclear and mitochondrial yeast DNA: comparison of wild-type and repair-deficient strains. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1722–1726. [PubMed]
  • Matsunaga T, Mu D, Park CH, Reardon JT, Sancar A. Human DNA repair excision nuclease. Analysis of the roles of the subunits involved in dual incisions by using anti-XPG and anti-ERCC1 antibodies. J Biol Chem. 1995 Sep 1;270(35):20862–20869. [PubMed]
  • Matsunaga T, Park CH, Bessho T, Mu D, Sancar A. Replication protein A confers structure-specific endonuclease activities to the XPF-ERCC1 and XPG subunits of human DNA repair excision nuclease. J Biol Chem. 1996 May 10;271(19):11047–11050. [PubMed]
  • Miller RD, Prakash L, Prakash S. Genetic control of excision of Saccharomyces cerevisiae interstrand DNA cross-links induced by psoralen plus near-UV light. Mol Cell Biol. 1982 Aug;2(8):939–948. [PMC free article] [PubMed]
  • Mu D, Park CH, Matsunaga T, Hsu DS, Reardon JT, Sancar A. Reconstitution of human DNA repair excision nuclease in a highly defined system. J Biol Chem. 1995 Feb 10;270(6):2415–2418. [PubMed]
  • Mu D, Hsu DS, Sancar A. Reaction mechanism of human DNA repair excision nuclease. J Biol Chem. 1996 Apr 5;271(14):8285–8294. [PubMed]
  • Mu D, Sancar A. Model for XPC-independent transcription-coupled repair of pyrimidine dimers in humans. J Biol Chem. 1997 Mar 21;272(12):7570–7573. [PubMed]
  • Mu D, Tursun M, Duckett DR, Drummond JT, Modrich P, Sancar A. Recognition and repair of compound DNA lesions (base damage and mismatch) by human mismatch repair and excision repair systems. Mol Cell Biol. 1997 Feb;17(2):760–769. [PMC free article] [PubMed]
  • Munn MM, Rupp WD. Interaction of the UvrABC endonuclease with DNA containing a psoralen monoadduct or cross-link. Differential effects of superhelical density and comparison of preincision complexes. J Biol Chem. 1991 Dec 25;266(36):24748–24756. [PubMed]
  • Park CH, Bessho T, Matsunaga T, Sancar A. Purification and characterization of the XPF-ERCC1 complex of human DNA repair excision nuclease. J Biol Chem. 1995 Sep 29;270(39):22657–22660. [PubMed]
  • Reardon JT, Spielmann P, Huang JC, Sastry S, Sancar A, Hearst JE. Removal of psoralen monoadducts and crosslinks by human cell free extracts. Nucleic Acids Res. 1991 Sep 11;19(17):4623–4629. [PMC free article] [PubMed]
  • Reardon JT, Thompson LH, Sancar A. Excision repair in man and the molecular basis of xeroderma pigmentosum syndrome. Cold Spring Harb Symp Quant Biol. 1993;58:605–617. [PubMed]
  • Saffran WA, Greenberg RB, Thaler-Scheer MS, Jones MM. Single strand and double strand DNA damage-induced reciprocal recombination in yeast. Dependence on nucleotide excision repair and RAD1 recombination. Nucleic Acids Res. 1994 Jul 25;22(14):2823–2829. [PMC free article] [PubMed]
  • Sage E, Drobetsky EA, Moustacchi E. 8-Methoxypsoralen induced mutations are highly targeted at crosslinkable sites of photoaddition on the non-transcribed strand of a mammalian chromosomal gene. EMBO J. 1993 Feb;12(2):397–402. [PubMed]
  • Sancar A. DNA excision repair. Annu Rev Biochem. 1996;65:43–81. [PubMed]
  • Sasaki MS, Tonomura A. A high susceptibility of Fanconi's anemia to chromosome breakage by DNA cross-linking agents. Cancer Res. 1973 Aug;33(8):1829–1836. [PubMed]
  • Schiestl RH, Prakash S. RAD1, an excision repair gene of Saccharomyces cerevisiae, is also involved in recombination. Mol Cell Biol. 1988 Sep;8(9):3619–3626. [PMC free article] [PubMed]
  • Schiestl RH, Prakash S. RAD10, an excision repair gene of Saccharomyces cerevisiae, is involved in the RAD1 pathway of mitotic recombination. Mol Cell Biol. 1990 Jun;10(6):2485–2491. [PMC free article] [PubMed]
  • Sekelsky JJ, McKim KS, Chin GM, Hawley RS. The Drosophila meiotic recombination gene mei-9 encodes a homologue of the yeast excision repair protein Rad1. Genetics. 1995 Oct;141(2):619–627. [PubMed]
  • Shi YB, Gamper H, Hearst JE. The effects of covalent additions of a psoralen on transcription by E. coli RNA polymerase. Nucleic Acids Res. 1987 Sep 11;15(17):6843–6854. [PMC free article] [PubMed]
  • Sladek FM, Munn MM, Rupp WD, Howard-Flanders P. In vitro repair of psoralen-DNA cross-links by RecA, UvrABC, and the 5'-exonuclease of DNA polymerase I. J Biol Chem. 1989 Apr 25;264(12):6755–6765. [PubMed]
  • Stahl F. Meiotic recombination in yeast: coronation of the double-strand-break repair model. Cell. 1996 Dec 13;87(6):965–968. [PubMed]
  • Sung P, Reynolds P, Prakash L, Prakash S. Purification and characterization of the Saccharomyces cerevisiae RAD1/RAD10 endonuclease. J Biol Chem. 1993 Dec 15;268(35):26391–26399. [PubMed]
  • Svoboda DL, Taylor JS, Hearst JE, Sancar A. DNA repair by eukaryotic nucleotide excision nuclease. Removal of thymine dimer and psoralen monoadduct by HeLa cell-free extract and of thymine dimer by Xenopus laevis oocytes. J Biol Chem. 1993 Jan 25;268(3):1931–1936. [PubMed]
  • Thompson LH. Evidence that mammalian cells possess homologous recombinational repair pathways. Mutat Res. 1996 Jun 12;363(2):77–88. [PubMed]
  • Tomkinson AE, Bardwell AJ, Bardwell L, Tappe NJ, Friedberg EC. Yeast DNA repair and recombination proteins Rad1 and Rad10 constitute a single-stranded-DNA endonuclease. Nature. 1993 Apr 29;362(6423):860–862. [PubMed]
  • Van Houten B, Gamper H, Holbrook SR, Hearst JE, Sancar A. Action mechanism of ABC excision nuclease on a DNA substrate containing a psoralen crosslink at a defined position. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8077–8081. [PubMed]
  • Vos JM, Hanawalt PC. Processing of psoralen adducts in an active human gene: repair and replication of DNA containing monoadducts and interstrand cross-links. Cell. 1987 Aug 28;50(5):789–799. [PubMed]
  • Vos JM, Hanawalt PC. DNA interstrand cross-links promote chromosomal integration of a selected gene in human cells. Mol Cell Biol. 1989 Jul;9(7):2897–2905. [PMC free article] [PubMed]
  • Vuksanovic L, Cleaver JE. Unique cross-link and monoadduct repair characteristics of a xeroderma pigmentosum revertant cell line. Mutat Res. 1987 Nov;184(3):255–263. [PubMed]
  • Wood RD. DNA repair in eukaryotes. Annu Rev Biochem. 1996;65:135–167. [PubMed]
  • Zamble DB, Mu D, Reardon JT, Sancar A, Lippard SJ. Repair of cisplatin--DNA adducts by the mammalian excision nuclease. Biochemistry. 1996 Aug 6;35(31):10004–10013. [PubMed]
  • Zdzienicka MZ. Mammalian mutants defective in the response to ionizing radiation-induced DNA damage. Mutat Res. 1995 May;336(3):203–213. [PubMed]
  • Zhen W, Evans MK, Haggerty CM, Bohr VA. Deficient gene specific repair of cisplatin-induced lesions in Xeroderma pigmentosum and Fanconi's anemia cell lines. Carcinogenesis. 1993 May;14(5):919–924. [PubMed]
  • Zwelling LA, Michaels S, Schwartz H, Dobson PP, Kohn KW. DNA cross-linking as an indicator of sensitivity and resistance of mouse L1210 leukemia to cis-diamminedichloroplatinum(II) and L-phenylalanine mustard. Cancer Res. 1981 Feb;41(2):640–649. [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)