Einzeltreffer — DigiBib

The presence of ribonucleotides in genomic DNA is undesirable given their increased susceptibility to hydrolysis. Ribonuclease (RNase) H enzymes that recognize and process such embedded ribonucleotides are present in all domains of life. However, in unicellular organisms such as budding yeast, they are not required for viability or even efficient cellular proliferation, while in humans, RNase H2 hypomorphic mutations cause the neuroinflammatory disorder Aicardi-Goutières syndrome. Here, we report that RNase H2 is an essential enzyme in mice, required for embryonic growth from gastrulation onward. RNase H2 null embryos accumulate large numbers of single (or di-) ribonucleotides embedded in their genomic DNA (>1,000,000 per cell), resulting in genome instability and a p53-dependent DNA-damage response. Our findings establish RNase H2 as a key mammalian genome surveillance enzyme required for ribonucleotide removal and demonstrate that ribonucleotides are the most commonly occurring endogenous nucleotide base lesion in replicating cells.

Titel:	Enzymatic removal of ribonucleotides from DNA is essential for mammalian genome integrity and development.
Autor/in / Beteiligte Person:	Reijns, MA ; Rabe, B ; Rigby, RE ; Mill, P ; Astell, KR ; Lettice, LA ; Boyle, S ; Leitch, A ; Keighren, M ; Kilanowski, F ; Devenney, PS ; Sexton, D ; Grimes, G ; Holt, IJ ; Hill, RE ; Taylor, MS ; Lawson, KA ; Dorin, JR ; Jackson, AP
Zeitschrift:	Cell, Jg. 149 (2012-05-25), Heft 5, S. 1008-22
Veröffentlichung:	Cambridge, Ma : Cell Press ; <i>Original Publication</i>: Cambridge, MIT Press., 2012
Medientyp:	academicJournal
ISSN:	1097-4172 (electronic)
DOI:	10.1016/j.cell.2012.04.011
Schlagwort:	Animals Chromosomal Instability DNA-Directed DNA Polymerase metabolism Embryonic Stem Cells metabolism Female Male Mice Mice, Inbred C57BL Tumor Suppressor Protein p53 genetics Tumor Suppressor Protein p53 metabolism DNA Replication Embryo, Mammalian metabolism Ribonuclease H genetics Ribonuclease H metabolism Ribonucleotides metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Cell] 2012 May 25; Vol. 149 (5), pp. 1008-22. <i>Date of Electronic Publication: </i>2012 May 10. MeSH Terms: DNA Replication* ; Embryo, Mammalian / metabolism ; Ribonuclease H / genetics ; Ribonuclease H / metabolism ; Ribonucleotides / metabolism ; Animals ; Chromosomal Instability ; DNA-Directed DNA Polymerase / metabolism ; Embryonic Stem Cells / metabolism ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Tumor Suppressor Protein p53 / genetics ; Tumor Suppressor Protein p53 / metabolism References: Proc Natl Acad Sci U S A. 1977 Jul;74(7):2776-9. (PMID: 268627) ; J Biol Chem. 2011 Mar 25;286(12):10530-9. (PMID: 21177854) ; Arthritis Rheum. 2010 May;62(5):1469-77. (PMID: 20131292) ; Trends Biochem Sci. 2009 Jul;34(7):358-65. (PMID: 19559620) ; Nat Genet. 2006 Aug;38(8):910-6. (PMID: 16845400) ; Nature. 2002 Dec 5;420(6915):520-62. (PMID: 12466850) ; J Biol Chem. 2011 Sep 9;286(36):31490-500. (PMID: 21778232) ; J Biol Chem. 1990 Apr 5;265(10):5561-6. (PMID: 1690712) ; IUBMB Life. 2003 Apr-May;55(4-5):213-7. (PMID: 12880201) ; Mutat Res. 2010 Apr-Jun;704(1-3):12-20. (PMID: 20096807) ; EMBO Rep. 2005 Apr;6(4):361-6. (PMID: 15776019) ; Cell. 2011 Oct 14;147(2):271-4. (PMID: 22000008) ; J Biol Chem. 1997 Sep 5;272(36):22591-9. (PMID: 9278414) ; Am J Hum Genet. 2007 Oct;81(4):713-25. (PMID: 17846997) ; J Mol Biol. 2010 Apr 16;397(5):1144-55. (PMID: 20184890) ; Oncogene. 2001 May 31;20(25):3290-300. (PMID: 11423978) ; J Biol Chem. 1989 Aug 25;264(24):14455-62. (PMID: 2760069) ; Hum Mol Genet. 2009 Oct 15;18(R2):R130-6. (PMID: 19808788) ; Cold Spring Harb Symp Quant Biol. 2000;65:127-33. (PMID: 12760027) ; Nat Rev Genet. 2008 Aug;9(8):619-31. (PMID: 18626472) ; Nat Genet. 1997 Jul;16(3):298-302. (PMID: 9207798) ; Nucleic Acids Res. 2011 May;39(9):3652-66. (PMID: 21245041) ; Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16654-9. (PMID: 12475934) ; J Pathol. 2011 May;224(1):10-21. (PMID: 21404276) ; Nat Chem Biol. 2010 Oct;6(10):774-81. (PMID: 20729855) ; Mol Cell. 2003 Sep;12(3):711-21. (PMID: 14527416) ; Curr Biol. 1995 Aug 1;5(8):931-6. (PMID: 7583151) ; Nat Genet. 2006 Aug;38(8):917-20. (PMID: 16845398) ; Nature. 1993 Apr 29;362(6423):849-52. (PMID: 8479523) ; J Biol Chem. 2006 Sep 8;281(36):26051-61. (PMID: 16837458) ; Cell. 2008 Aug 22;134(4):569-71. (PMID: 18724930) ; J Biol Chem. 1990 Oct 25;265(30):18461-71. (PMID: 2170412) ; Curr Biol. 2000 Oct 5;10(19):1221-4. (PMID: 11050393) ; DNA Repair (Amst). 2007 Feb 4;6(2):224-34. (PMID: 17116431) ; Cell. 1999 Oct 29;99(3):247-57. (PMID: 10555141) ; J Biol Chem. 2001 Dec 21;276(51):47759-62. (PMID: 11673449) ; Genesis. 2004 Mar;38(3):151-8. (PMID: 15048813) ; J Biol Chem. 1980 Oct 10;255(19):9434-43. (PMID: 6251088) ; Genes Cells. 2000 Oct;5(10):789-802. (PMID: 11029655) ; J Biol Chem. 2011 Mar 25;286(12):10540-50. (PMID: 21177858) ; Biochimie. 1993;75(1-2):123-6. (PMID: 8389211) ; PLoS Genet. 2011 Dec;7(12):e1002407. (PMID: 22144917) ; Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9803-7. (PMID: 7524089) ; Development. 2007 Mar;134(5):909-19. (PMID: 17251268) ; Nat Genet. 2010 Jan;42(1):89-93. (PMID: 20023660) ; Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1619-22. (PMID: 9050827) ; J Immunol. 2011 Nov 15;187(10):5336-45. (PMID: 22013119) ; J Biol Chem. 2010 Feb 5;285(6):3617-3624. (PMID: 19923215) ; Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):4949-54. (PMID: 20194773) ; Science. 1969 Oct 17;166(3903):393-5. (PMID: 5812039) ; Cold Spring Harb Perspect Biol. 2010 Jun;2(6):a001198. (PMID: 20516129) ; Genes Dev. 1999 Jan 15;13(2):152-7. (PMID: 9925639) ; Nature. 1992 Mar 26;356(6367):356-8. (PMID: 1549180) ; Nat Genet. 2009 Jul;41(7):829-32. (PMID: 19525956) ; FEBS J. 2009 Mar;276(6):1494-505. (PMID: 19228196) ; Curr Biol. 2000 Oct 5;10(19):1217-20. (PMID: 11050392) ; Genes Dev. 2010 Jul 15;24(14):1546-58. (PMID: 20634320) ; J Biol Chem. 2010 Aug 6;285(32):24457-65. (PMID: 20519499) ; Science. 2011 Jun 24;332(6037):1561-4. (PMID: 21700875) ; Bioinformatics. 2007 Aug 15;23(16):2183-4. (PMID: 17586828) ; Mol Cell. 1997 Dec;1(1):89-97. (PMID: 9659906) ; Cell. 1977 Aug;11(4):719-27. (PMID: 560914) ; Brief Funct Genomic Proteomic. 2007 Sep;6(3):180-5. (PMID: 17967808) ; Mol Cell. 2012 Jan 13;45(1):99-110. (PMID: 22244334) ; Proc Natl Acad Sci U S A. 1973 Dec;70(12):3339-43. (PMID: 4202844) ; Nucleic Acids Res. 2009 Jan;37(1):96-110. (PMID: 19015152) ; J Biol Chem. 2009 Feb 13;284(7):4041-5. (PMID: 18835809) ; Chromosoma. 1994 Mar;103(1):46-55. (PMID: 8013255) ; DNA Repair (Amst). 2011 Aug 15;10(8):897-902. (PMID: 21703943) ; Mol Cell. 2003 Mar;11(3):807-15. (PMID: 12667461) ; Development. 1993 Mar;117(3):873-83. (PMID: 8325243) ; Mutagenesis. 2003 May;18(3):221-33. (PMID: 12714687) ; Cold Spring Harb Perspect Biol. 2012 Jul 01;4(7):a006742. (PMID: 21441585) ; EMBO Rep. 2006 Jan;7(1):59-65. (PMID: 16299470) ; Methods. 2001 Dec;25(4):402-8. (PMID: 11846609) ; Mol Cell. 2010 Oct 22;40(2):179-204. (PMID: 20965415) ; Mol Cell Biol. 2006 Oct;26(20):7520-8. (PMID: 16908529) ; Cell. 2005 Aug 12;122(3):365-78. (PMID: 16096057) ; Mol Cell. 2007 Oct 26;28(2):264-76. (PMID: 17964265) ; Stat Appl Genet Mol Biol. 2004;3:Article3. (PMID: 16646809) ; Nucleic Acids Res. 2004 Jan 20;32(2):407-14. (PMID: 14734815) ; Genes Dev. 2004 Apr 1;18(7):794-804. (PMID: 15059961) ; Cell. 2008 Aug 22;134(4):587-98. (PMID: 18724932) ; Nat Genet. 1995 Jun;10(2):175-80. (PMID: 7663512) ; Trends Cell Biol. 2008 Nov;18(11):521-7. (PMID: 18824354) ; Cell. 2007 Nov 30;131(5):873-86. (PMID: 18045533) ; J Biol Chem. 1998 Mar 6;273(10):5858-68. (PMID: 9488723) Grant Information: MC_U127597124 United Kingdom MRC_ Medical Research Council; MC_PC_U127580972 United Kingdom MRC_ Medical Research Council; MC_U127584494 United Kingdom MRC_ Medical Research Council; United Kingdom WT_ Wellcome Trust; MC_U105663140 United Kingdom MRC_ Medical Research Council; MC_PC_U127597124 United Kingdom MRC_ Medical Research Council Molecular Sequence: GEO GSE37419 Substance Nomenclature: 0 (Ribonucleotides) ; 0 (Tumor Suppressor Protein p53) ; EC 2.7.7.7 (DNA-Directed DNA Polymerase) ; EC 3.1.26.4 (Ribonuclease H) Entry Date(s): Date Created: 20120515 Date Completed: 20120730 Latest Revision: 20240629 Update Code: 20240629 PubMed Central ID: PMC3383994

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Enzymatic removal of ribonucleotides from DNA is essential for mammalian genome integrity and development.