Genomic assay reveals tolerance of DNA damage by both translesion DNA synthesis and homology-dependent repair in mammalian cells
DNA lesions can block replication forks and lead to the formation of single-stranded gaps. These replication complications are mitigated by DNA damage tolerance mechanisms, which prevent deleterious outcomes such as cell death, genomic instability, and carcinogenesis. The two main tolerance strategi...
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| Published in: | Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 16; p. E1462 |
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| Main Authors: | , , , , |
| Format: | Journal Article |
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16.04.2013
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| ISSN: | 1091-6490, 1091-6490 |
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| Abstract | DNA lesions can block replication forks and lead to the formation of single-stranded gaps. These replication complications are mitigated by DNA damage tolerance mechanisms, which prevent deleterious outcomes such as cell death, genomic instability, and carcinogenesis. The two main tolerance strategies are translesion DNA synthesis (TLS), in which low-fidelity DNA polymerases bypass the blocking lesion, and homology-dependent repair (HDR; postreplication repair), which is based on the homologous sister chromatid. Here we describe a unique high-resolution method for the simultaneous analysis of TLS and HDR across defined DNA lesions in mammalian genomes. The method is based on insertion of plasmids carrying defined site-specific DNA lesions into mammalian chromosomes, using phage integrase-mediated integration. Using this method we show that mammalian cells use HDR to tolerate DNA damage in their genome. Moreover, analysis of the tolerance of the UV light-induced 6-4 photoproduct, the tobacco smoke-induced benzo[a]pyrene-guanine adduct, and an artificial trimethylene insert shows that each of these three lesions is tolerated by both TLS and HDR. We also determined the specificity of nucleotide insertion opposite these lesions during TLS in human genomes. This unique method will be useful in elucidating the mechanism of DNA damage tolerance in mammalian chromosomes and their connection to pathological processes such as carcinogenesis. |
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| AbstractList | DNA lesions can block replication forks and lead to the formation of single-stranded gaps. These replication complications are mitigated by DNA damage tolerance mechanisms, which prevent deleterious outcomes such as cell death, genomic instability, and carcinogenesis. The two main tolerance strategies are translesion DNA synthesis (TLS), in which low-fidelity DNA polymerases bypass the blocking lesion, and homology-dependent repair (HDR; postreplication repair), which is based on the homologous sister chromatid. Here we describe a unique high-resolution method for the simultaneous analysis of TLS and HDR across defined DNA lesions in mammalian genomes. The method is based on insertion of plasmids carrying defined site-specific DNA lesions into mammalian chromosomes, using phage integrase-mediated integration. Using this method we show that mammalian cells use HDR to tolerate DNA damage in their genome. Moreover, analysis of the tolerance of the UV light-induced 6-4 photoproduct, the tobacco smoke-induced benzo[a]pyrene-guanine adduct, and an artificial trimethylene insert shows that each of these three lesions is tolerated by both TLS and HDR. We also determined the specificity of nucleotide insertion opposite these lesions during TLS in human genomes. This unique method will be useful in elucidating the mechanism of DNA damage tolerance in mammalian chromosomes and their connection to pathological processes such as carcinogenesis.DNA lesions can block replication forks and lead to the formation of single-stranded gaps. These replication complications are mitigated by DNA damage tolerance mechanisms, which prevent deleterious outcomes such as cell death, genomic instability, and carcinogenesis. The two main tolerance strategies are translesion DNA synthesis (TLS), in which low-fidelity DNA polymerases bypass the blocking lesion, and homology-dependent repair (HDR; postreplication repair), which is based on the homologous sister chromatid. Here we describe a unique high-resolution method for the simultaneous analysis of TLS and HDR across defined DNA lesions in mammalian genomes. The method is based on insertion of plasmids carrying defined site-specific DNA lesions into mammalian chromosomes, using phage integrase-mediated integration. Using this method we show that mammalian cells use HDR to tolerate DNA damage in their genome. Moreover, analysis of the tolerance of the UV light-induced 6-4 photoproduct, the tobacco smoke-induced benzo[a]pyrene-guanine adduct, and an artificial trimethylene insert shows that each of these three lesions is tolerated by both TLS and HDR. We also determined the specificity of nucleotide insertion opposite these lesions during TLS in human genomes. This unique method will be useful in elucidating the mechanism of DNA damage tolerance in mammalian chromosomes and their connection to pathological processes such as carcinogenesis. DNA lesions can block replication forks and lead to the formation of single-stranded gaps. These replication complications are mitigated by DNA damage tolerance mechanisms, which prevent deleterious outcomes such as cell death, genomic instability, and carcinogenesis. The two main tolerance strategies are translesion DNA synthesis (TLS), in which low-fidelity DNA polymerases bypass the blocking lesion, and homology-dependent repair (HDR; postreplication repair), which is based on the homologous sister chromatid. Here we describe a unique high-resolution method for the simultaneous analysis of TLS and HDR across defined DNA lesions in mammalian genomes. The method is based on insertion of plasmids carrying defined site-specific DNA lesions into mammalian chromosomes, using phage integrase-mediated integration. Using this method we show that mammalian cells use HDR to tolerate DNA damage in their genome. Moreover, analysis of the tolerance of the UV light-induced 6-4 photoproduct, the tobacco smoke-induced benzo[a]pyrene-guanine adduct, and an artificial trimethylene insert shows that each of these three lesions is tolerated by both TLS and HDR. We also determined the specificity of nucleotide insertion opposite these lesions during TLS in human genomes. This unique method will be useful in elucidating the mechanism of DNA damage tolerance in mammalian chromosomes and their connection to pathological processes such as carcinogenesis. |
| Author | Ziv, Omer Cohen, Isadora S Livneh, Zvi Izhar, Lior Geacintov, Nicholas E |
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| References | 16247017 - Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15954-9 19153606 - EMBO J. 2009 Feb 18;28(4):383-93 10385124 - Nature. 1999 Jun 17;399(6737):700-4 10029669 - Mutat Res. 1999 Jan 25;423(1-2):23-32 18634905 - DNA Repair (Amst). 2008 Oct 1;7(10):1636-46 20139724 - Cell Cycle. 2010 Feb 15;9(4):729-35 9665722 - Biochemistry. 1998 Jul 14;37(28):10164-72 10231549 - Biochemistry. 1999 May 4;38(18):5948-58 19079240 - Nature. 2009 Jan 29;457(7229):612-5 1632522 - Anal Biochem. 1992 Mar;201(2):331-5 19729992 - Cell Cycle. 2009 Sep 15;8(18):2857-8 20403322 - Cell. 2010 Apr 16;141(2):255-67 19654238 - Nucleic Acids Res. 2009 Sep;37(17):5737-48 15475561 - J Biol Chem. 2004 Dec 17;279(51):53298-305 7821287 - Environ Health Perspect. 1994 Oct;102 Suppl 4:135-8 16337601 - Mol Cell. 2005 Dec 9;20(5):783-92 16678112 - Mol Cell. 2006 May 5;22(3):407-13 20080950 - Genes Dev. 2010 Jan 15;24(2):123-8 11917106 - Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4459-64 17936713 - Mol Cell. 2007 Oct 12;28(1):167-75 20453836 - Nature. 2010 Jun 17;465(7300):951-5 12459444 - Mutat Res. 2002 Dec 29;510(1-2):71-80 12419234 - Mol Cell. 2002 Oct;10(4):917-24 15952890 - Annu Rev Biochem. 2005;74:317-53 18157155 - Cell Res. 2008 Jan;18(1):174-83 20660785 - Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14116-21 16341080 - Nat Rev Mol Cell Biol. 2005 Dec;6(12):943-53 16956796 - DNA Repair (Amst). 2006 Dec 9;5(12):1495-8 8657563 - Nucleic Acids Res. 1996 May 15;24(10):1837-40 17898175 - Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15591-8 4947693 - J Mol Biol. 1971 Oct 14;61(1):25-44 21926160 - Nucleic Acids Res. 2012 Jan;40(2):682-91 19092928 - Nature. 2008 Dec 18;456(7224):915-20 3278320 - Proc Natl Acad Sci U S A. 1988 Mar;85(5):1586-9 19948885 - Mol Cell Biol. 2010 Feb;30(3):684-93 18585391 - J Mol Biol. 2008 Sep 12;381(4):803-9 16971464 - Nucleic Acids Res. 2006;34(17):4731-42 18953031 - Nucleic Acids Res. 2008 Dec;36(21):6767-80 16414067 - J Mol Biol. 2006 Mar 17;357(1):28-48 21908406 - Nucleic Acids Res. 2012 Jan;40(1):170-80 22798494 - Nucleic Acids Res. 2012 Oct;40(18):9036-43 16473566 - DNA Repair (Amst). 2006 Apr 8;5(4):479-90 19564618 - Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11552-7 12226657 - Nature. 2002 Sep 12;419(6903):135-41 3104770 - Mol Cell Biol. 1987 Mar;7(3):1267-70 10398605 - Science. 1999 Jul 9;285(5425):263-5 15551273 - Bioessays. 2004 Dec;26(12):1322-6 16969082 - Cell Cycle. 2006 Sep;5(17):1918-22 22532806 - PLoS Genet. 2012;8(4):e1002659 11554790 - J Mol Biol. 2001 Sep 14;312(2):335-46 16397225 - Cancer Res. 2006 Jan 1;66(1):134-42 20159558 - Mol Cell. 2010 Feb 12;37(3):396-407 14657386 - Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14760-5 |
| References_xml | – reference: 10398605 - Science. 1999 Jul 9;285(5425):263-5 – reference: 16397225 - Cancer Res. 2006 Jan 1;66(1):134-42 – reference: 21908406 - Nucleic Acids Res. 2012 Jan;40(1):170-80 – reference: 11917106 - Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4459-64 – reference: 19654238 - Nucleic Acids Res. 2009 Sep;37(17):5737-48 – reference: 22798494 - Nucleic Acids Res. 2012 Oct;40(18):9036-43 – reference: 17898175 - Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15591-8 – reference: 17936713 - Mol Cell. 2007 Oct 12;28(1):167-75 – reference: 19948885 - Mol Cell Biol. 2010 Feb;30(3):684-93 – reference: 16969082 - Cell Cycle. 2006 Sep;5(17):1918-22 – reference: 18585391 - J Mol Biol. 2008 Sep 12;381(4):803-9 – reference: 19153606 - EMBO J. 2009 Feb 18;28(4):383-93 – reference: 15551273 - Bioessays. 2004 Dec;26(12):1322-6 – reference: 16341080 - Nat Rev Mol Cell Biol. 2005 Dec;6(12):943-53 – reference: 3278320 - Proc Natl Acad Sci U S A. 1988 Mar;85(5):1586-9 – reference: 10029669 - Mutat Res. 1999 Jan 25;423(1-2):23-32 – reference: 19092928 - Nature. 2008 Dec 18;456(7224):915-20 – reference: 16473566 - DNA Repair (Amst). 2006 Apr 8;5(4):479-90 – reference: 12226657 - Nature. 2002 Sep 12;419(6903):135-41 – reference: 16971464 - Nucleic Acids Res. 2006;34(17):4731-42 – reference: 20660785 - Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14116-21 – reference: 3104770 - Mol Cell Biol. 1987 Mar;7(3):1267-70 – reference: 16678112 - Mol Cell. 2006 May 5;22(3):407-13 – reference: 20080950 - Genes Dev. 2010 Jan 15;24(2):123-8 – reference: 21926160 - Nucleic Acids Res. 2012 Jan;40(2):682-91 – reference: 15952890 - Annu Rev Biochem. 2005;74:317-53 – reference: 22532806 - PLoS Genet. 2012;8(4):e1002659 – reference: 18634905 - DNA Repair (Amst). 2008 Oct 1;7(10):1636-46 – reference: 1632522 - Anal Biochem. 1992 Mar;201(2):331-5 – reference: 18953031 - Nucleic Acids Res. 2008 Dec;36(21):6767-80 – reference: 16956796 - DNA Repair (Amst). 2006 Dec 9;5(12):1495-8 – reference: 19564618 - Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11552-7 – reference: 19729992 - Cell Cycle. 2009 Sep 15;8(18):2857-8 – reference: 10231549 - Biochemistry. 1999 May 4;38(18):5948-58 – reference: 15475561 - J Biol Chem. 2004 Dec 17;279(51):53298-305 – reference: 10385124 - Nature. 1999 Jun 17;399(6737):700-4 – reference: 20453836 - Nature. 2010 Jun 17;465(7300):951-5 – reference: 18157155 - Cell Res. 2008 Jan;18(1):174-83 – reference: 8657563 - Nucleic Acids Res. 1996 May 15;24(10):1837-40 – reference: 16247017 - Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):15954-9 – reference: 11554790 - J Mol Biol. 2001 Sep 14;312(2):335-46 – reference: 9665722 - Biochemistry. 1998 Jul 14;37(28):10164-72 – reference: 20139724 - Cell Cycle. 2010 Feb 15;9(4):729-35 – reference: 12419234 - Mol Cell. 2002 Oct;10(4):917-24 – reference: 20159558 - Mol Cell. 2010 Feb 12;37(3):396-407 – reference: 16414067 - J Mol Biol. 2006 Mar 17;357(1):28-48 – reference: 20403322 - Cell. 2010 Apr 16;141(2):255-67 – reference: 16337601 - Mol Cell. 2005 Dec 9;20(5):783-92 – reference: 19079240 - Nature. 2009 Jan 29;457(7229):612-5 – reference: 7821287 - Environ Health Perspect. 1994 Oct;102 Suppl 4:135-8 – reference: 4947693 - J Mol Biol. 1971 Oct 14;61(1):25-44 – reference: 12459444 - Mutat Res. 2002 Dec 29;510(1-2):71-80 – reference: 14657386 - Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14760-5 |
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| SubjectTerms | Benzo(a)pyrene - metabolism DNA Adducts - metabolism DNA Damage - physiology DNA Repair - physiology DNA Replication - physiology DNA-Directed DNA Polymerase - metabolism Genomics - methods Humans Plasmids - genetics Sequence Homology Ultraviolet Rays |
| Title | Genomic assay reveals tolerance of DNA damage by both translesion DNA synthesis and homology-dependent repair in mammalian cells |
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