title: Psoralen-induced DNA adducts are substrates for the base excision repair pathway in human cells.
abstract: Interstrand cross-link (ICL) is a covalent modification of both strands of DNA, which prevents DNA strand separation during transcription and replication. Upon photoactivation 8-methoxypsoralen (8-MOP+UVA) alkylates both strands of DNA duplex at the 5,6-double bond of thymidines, generating monoadducts (MAs) and ICLs. It was thought that bulky DNA lesions such as MAs are eliminated only in the nucleotide excision repair pathway. Instead, non-bulky DNA lesions are substrates for DNA glycosylases and AP endonucleases which initiate the base excision repair (BER) pathway. Here we examined whether BER might be involved in the removal of psoralen-DNA photoadducts. The results show that in human cells DNA glycosylase NEIL1 excises the MAs in duplex DNA, subsequently the apurinic/apyrimidinic endonuclease 1, APE1, removes the 3'-phosphate residue at single-strand break generated by NEIL1. The apparent kinetic parameters suggest that NEIL1 excises MAs with high efficiency. Consistent with these results HeLa cells lacking APE1 and/or NEIL1 become hypersensitive to 8-MOP+UVA exposure. Furthermore, we demonstrate that bacterial homologues of NEIL1, the Fpg and Nei proteins, also excise MAs. New substrate specificity of the Fpg/Nei protein family provides an alternative repair pathway for ICLs and bulky DNA damage.
authors: Group DNA repair, UMR 8126 of CNRS and Group FANC/BRCA pathway and Cancer FRE2939 of CNRS, University of Paris-South, Institute Gustave Roussy, Villejuif Cedex, F-94805, France.
authors: Sophie
authors: S
authors: Couvé-Privat
authors: Gaëtane
authors: G
authors: Macé
authors: Filippo
authors: F
authors: Rosselli
authors: Murat K
authors: MK
authors: Saparbaev
mesh_terms: D003432:Cross-Linking Reagents; D018736:DNA Adducts / Q000378:metabolism*; D045647:DNA Glycosylases / Q000378:metabolism*; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism*; D043382:DNA-Formamidopyrimidine Glycosylase / Q000378:metabolism; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins / Q000378:metabolism; D011564:Furocoumarins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D003432:Cross-Linking Reagents; D018736:DNA Adducts; D029968:Escherichia coli Proteins; D011564:Furocoumarins; D009838:Oligodeoxyribonucleotides; D010710:Phosphates; C056465:psoralen-DNA adduct; D043224:Deoxyribonuclease (Pyrimidine Dimer); C468346:Nei protein, E coli; D045647:DNA Glycosylases; C473634:NEIL1 protein, human; D043382:DNA-Formamidopyrimidine Glycosylase; C468610:DNA-formamidopyrimidine glycosylase, E coli; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
references: Biochim Biophys Acta. 1971 Nov 29;254(1):30-9
references: 5167399
references: J Biol Chem. 2007 Sep 7;282(36):26591-602
references: 17611195
references: J Biol Chem. 1977 Oct 25;252(20):7023-30
references: 332687
references: Biochemistry. 1981 Feb 17;20(4):739-45
references: 7213609
references: Mol Cell. 2004 Jul 23;15(2):209-20
references: 15260972
references: DNA Repair (Amst). 2004 Dec 2;3(12):1579-90
references: 15474419
references: Cancer Res. 1985 Apr;45(4):1737-43
references: 3919945
references: Food Addit Contam. 1985 Jan-Mar;2(1):25-32
references: 4018311
references: Annu Rev Biochem. 1985;54:1151-93
references: 2411210
references: J Biol Chem. 1988 Nov 15;263(32):16553-60
references: 3053693
references: Proc Natl Acad Sci U S A. 1988 Nov;85(22):8410-4
references: 3054888
references: Proc Natl Acad Sci U S A. 1989 Jul;86(14):5222-6
references: 2664776
references: Nucleic Acids Res. 1991 Feb 11;19(3):657-63
references: 2011535
references: Nucleic Acids Res. 1991 Nov 11;19(21):5907-14
references: 1719484
references: J Biol Chem. 1993 Jan 25;268(3):1931-6
references: 8420966
references: Nucleic Acids Res. 1994 Nov 25;22(23):4884-9
references: 7800476
references: J Biol Chem. 1995 Aug 18;270(33):19501-8
references: 7642635
references: Cell. 1995 Dec 1;83(5):773-82
references: 8521494
references: Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13737-41
references: 8943004
references: J Bacteriol. 1997 Jun;179(11):3773-82
references: 9171429
references: J Bacteriol. 1997 Jun;179(11):3783-5
references: 9171430
references: J Biol Chem. 1997 Dec 19;272(51):32230-9
references: 9405426
references: Nat Struct Biol. 1998 Dec;5(12):1058-64
references: 9846876
references: Annu Rev Genet. 2004;38:445-76
references: 15568983
references: Carcinogenesis. 2004 Dec;25(12):2311-7
references: 15319300
references: Mol Cell Biol. 2005 Aug;25(15):6380-90
references: 16024777
references: Nature. 2000 Feb 24;403(6772):859-66
references: 10706276
references: Mol Cell Biol. 2000 Apr;20(7):2446-54
references: 10713168
references: Arch Biochem Biophys. 2000 May 1;377(1):1-8
references: 10775435
references: Mol Cell Biol. 2001 Feb;21(3):713-20
references: 11154259
references: Mutat Res. 2001 Sep 4;486(4):217-47
references: 11516927
references: Environ Mol Mutagen. 2001;38(2-3):227-34
references: 11746759
references: Biochemistry. 2002 Jan 22;41(3):890-6
references: 11790111
references: EMBO J. 2002 Feb 15;21(4):789-800
references: 11847126
references: Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3523-8
references: 11904416
references: FASEB J. 2002 May;16(7):757-8
references: 11978740
references: J Biol Chem. 2002 May 31;277(22):19811-6
references: 11912217
references: Nucleic Acids Res. 2002 Nov 15;30(22):4926-36
references: 12433996
references: DNA Repair (Amst). 2002 Jul 17;1(7):517-29
references: 12509226
references: DNA Repair (Amst). 2003 May 13;2(5):581-91
references: 12713815
references: Nucleic Acids Res. 2003 Nov 1;31(21):6344-53
references: 14576322
references: J Biol Chem. 2003 Dec 12;278(50):49679-84
references: 14522990
references: Nucleic Acids Res. 2004;32(1):73-81
references: 14704345
references: EMBO J. 2004 Mar 10;23(5):1178-87
references: 14988723
references: J Biol Chem. 2004 Apr 2;279(14):14464-71
references: 14734554
references: Mol Cell Biol. 2004 Jul;24(13):5776-87
references: 15199134
references: Mol Cancer Ther. 2004 Jun;3(6):679-86
references: 15210853
references: Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10284-9
references: 15232006
references: Biochemistry. 2005 Aug 9;44(31):10613-9
references: 16060670
references: Nucleic Acids Res. 2005;33(15):4849-56
references: 16129732
references: J Biol Chem. 2005 Oct 21;280(42):35272-80
references: 16118226
references: Genes Dev. 2005 Dec 15;19(24):2925-40
references: 16357213
references: Cell. 2005 Dec 29;123(7):1191-8
references: 16377561
references: Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1864-9
references: 16446448
references: EMBO J. 2006 Oct 18;25(20):4921-32
references: 17036055
references: DNA Repair (Amst). 2006 Dec 9;5(12):1439-48
references: 16982218
references: DNA Repair (Amst). 2007 Jan 4;6(1):8-18
references: 16978929
references: Biochemistry. 2007 Apr 3;46(13):4158-63
references: 17348689
references: J Biol Chem. 2007 May 25;282(21):15790-8
references: 17389588
references: Proc Natl Acad Sci U S A. 1973 Apr;70(4):1064-8
references: 4577788