title: Translesion synthesis of 8,5'-cyclopurine-2'-deoxynucleosides by DNA polymerases η, ι, and ζ.
abstract: Reactive oxygen species can give rise to a battery of DNA damage products including the 8,5'-cyclo-2'-deoxyadenosine (cdA) and 8,5'-cyclo-2'-deoxyguanosine (cdG) tandem lesions. The 8,5'-cyclopurine-2'-deoxynucleosides are quite stable lesions and are valid and reliable markers of oxidative DNA damage. However, it remains unclear how these lesions compromise DNA replication in mammalian cells. Previous in vitro biochemical assays have suggested a role for human polymerase (Pol) η in the insertion step of translesion synthesis (TLS) across the (5'S) diastereomers of cdA and cdG. Using in vitro steady-state kinetic assay, herein we showed that human Pol ι and a two-subunit yeast Pol ζ complex (REV3/REV7) could function efficiently in the insertion and extension steps, respectively, of TLS across S-cdA and S-cdG; human Pol κ and Pol η could also extend past these lesions, albeit much less efficiently. Results from a quantitative TLS assay showed that, in human cells, S-cdA and S-cdG inhibited strongly DNA replication and induced substantial frequencies of mutations at the lesion sites. Additionally, Pol η, Pol ι, and Pol ζ, but not Pol κ, had important roles in promoting replication through S-cdA and S-cdG in human cells. Based on these results, we propose a model for TLS across S-cdA and S-cdG in human cells, where Pol η and/or Pol ι carries out nucleotide insertion opposite the lesion, whereas Pol ζ executes the extension step.
authors: From the Department of Chemistry and.
authors: Changjun
authors: C
authors: You
authors: Ashley L
authors: AL
authors: Swanson
authors: Xiaoxia
authors: X
authors: Dai
authors: Bifeng
authors: B
authors: Yuan
authors: Jianshuang
authors: J
authors: Wang
authors: Yinsheng
authors: Y
authors: Wang
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000096:biosynthesis*; D018736:DNA Adducts; D004249:DNA Damage; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D003839:Deoxyadenosines / Q000737:chemistry / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D000094769:DNA Polymerase iota; D000099270:Y-Family DNA Polymerases
chemical_list: D004247:DNA; D018736:DNA Adducts; D004259:DNA-Directed DNA Polymerase; D003839:Deoxyadenosines; D003849:Deoxyguanosine; D034741:RNA, Small Interfering; D000094769:DNA Polymerase iota; C050888:8,5'-cyclo-2'-deoxyguanosine; C056752:8,5'-cyclo-2'-deoxyadenosine; C425929:DNA polymerase zeta; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases
keywords: DNA Damage; DNA Polymerase; DNA Replication; Mutagenesis Site Specific; Oxygen Radicals
references: Aging Cell. 2012 Aug;11(4):714-6
references: 22530741
references: EMBO J. 2003 Dec 15;22(24):6621-30
references: 14657033
references: Genes Dev. 2010 Jan 15;24(2):123-8
references: 20080950
references: Cell Res. 2008 Jan;18(1):174-83
references: 18157155
references: Nature. 2012 Nov 15;491(7424):449-53
references: 23123854
references: Chem Soc Rev. 2011 Mar;40(3):1368-82
references: 21221459
references: Chem Res Toxicol. 2008 Feb;21(2):276-81
references: 18189366
references: Anal Chem. 2011 Mar 15;83(6):2201-9
references: 21323344
references: Chem Res Toxicol. 2012 Nov 19;25(11):2523-31
references: 23113558
references: Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):3832-7
references: 10759556
references: DNA Repair (Amst). 2008 Sep 1;7(9):1413-25
references: 18603018
references: J Biol Chem. 2012 Nov 30;287(49):40915-23
references: 23076150
references: Cell Cycle. 2010 Feb 15;9(4):729-35
references: 20139724
references: Biochemistry. 2011 May 17;50(19):3862-5
references: 21491964
references: Environ Mol Mutagen. 2011 May;52(4):287-95
references: 20872830
references: J Biol Chem. 2001 Dec 28;276(52):49283-8
references: 11677235
references: J Cell Sci. 1992 Dec;103 ( Pt 4):907-18
references: 1336780
references: Chem Res Toxicol. 1999 May;12(5):412-21
references: 10328751
references: Nat Rev Mol Cell Biol. 2012 Feb 23;13(3):141-52
references: 22358330
references: J Biol Chem. 2011 May 20;286(20):17503-11
references: 21454642
references: Genes Chromosomes Cancer. 2001 Nov;32(3):222-35
references: 11579462
references: Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11552-7
references: 19564618
references: Proc Natl Acad Sci U S A. 2012 Aug 28;109(35):14007-12
references: 22893683
references: Methods Enzymol. 2006;408:1-15
references: 16793359
references: DNA Repair (Amst). 2008 Jul 1;7(7):1168-79
references: 18495558
references: Nucleic Acids Res. 2012 Dec;40(22):11618-26
references: 23066099
references: Genes Cells. 2004 Jun;9(6):523-31
references: 15189446
references: Chem Res Toxicol. 2012 Aug 20;25(8):1682-91
references: 22768970
references: Cancer Res. 2000 Aug 1;60(15):4098-104
references: 10945616
references: Nat Rev Cancer. 2011 Feb;11(2):96-110
references: 21258395
references: Nat Chem Biol. 2012 Oct;8(10):817-22
references: 22902614
references: Mutat Res. 2003 Oct 29;531(1-2):5-23
references: 14637244
references: Biochim Biophys Acta. 2009 Oct;1790(10):963-9
references: 19344750
references: Nucleic Acids Res. 2010 Dec;38(22):8178-87
references: 20702424
references: Chem Res Toxicol. 2002 Feb;15(2):160-4
references: 11849041
references: Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12455-60
references: 22711820
references: DNA Repair (Amst). 2012 Nov 1;11(11):926-31
references: 23063091
references: J Biol Chem. 2000 Jul 21;275(29):22355-62
references: 10801836
references: EMBO J. 2009 Feb 18;28(4):383-93
references: 19153606
references: J Biol Chem. 2003 Apr 4;278(14):12356-60
references: 12529368
references: Nucleic Acids Res. 1989 Apr 11;17(7):2503-16
references: 2785681
references: J Biol Chem. 2007 Aug 3;282(31):22592-604
references: 17507378
references: J Virol Methods. 2004 Dec 1;122(1):123-7
references: 15488630
references: Nucleic Acids Res. 2011 Aug;39(14):5945-54
references: 21470959
references: DNA Repair (Amst). 2002 Nov 3;1(11):967-75
references: 12531024
references: Oncogene. 2007 Aug 23;26(39):5713-21
references: 17369853
references: DNA Repair (Amst). 2006 Aug 13;5(8):986-96
references: 16955546
references: Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14051-6
references: 15381779
references: J Biol Chem. 2001 Sep 21;276(38):35644-51
references: 11485998
references: Virology. 2003 Oct 10;315(1):103-9
references: 14592763
references: Crit Rev Biochem Mol Biol. 1993;28(2):83-126
references: 8485987
references: Nature. 1993 Apr 22;362(6422):709-15
references: 8469282
references: Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14116-21
references: 20660785