title: Silenced yeast chromatin is maintained by Sir2 in preference to permitting histone acetylations for efficient NER.
abstract: Very little is currently known about how nucleotide excision repair (NER) functions at the ends of chromosomes. To examine this, we introduced the URA3 gene into either transcriptionally active or repressed subtelomeric regions of the yeast genome. This enabled us to examine the repair of ultraviolet (UV)-induced cyclobutane pyrimidine dimers (CPDs) in identical sequences under both circumstances. We found that NER is significantly more efficient in the non-repressed subtelomere than the repressed one. At the non-repressed subtelomere, UV radiation stimulates both histones H3 and H4 acetylation in a similar fashion to that seen at other regions of the yeast genome. These modifications occur regardless of the presence of the Sir2 histone deacetylase. On the other hand, at the repressed subtelomere, where repair is much less efficient, UV radiation is unable to stimulate histone H4 or H3 acetylation in the presence of Sir2. In the absence of Sir2 both of these UV-induced modifications are detected, resulting in a significant increase in NER efficiency in the region. Our experiments reveal that there are instances in the yeast genome where the maintenance of the existing chromatin structures dominates over the action of chromatin modifications associated with efficient NER.
authors.affiliation: Department of Pathology, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Agurtzane
authors.initials: A
authors.lastname: Irizar
authors.forename: Yachuan
authors.initials: Y
authors.lastname: Yu
authors.forename: Simon H
authors.initials: SH
authors.lastname: Reed
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Louis
authors.forename: Raymond
authors.initials: R
authors.lastname: Waters
mesh_terms: D000107:Acetylation; D002453:Cell Cycle / Q000528:radiation effects; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D015825:Chromosomes, Fungal; D004260:DNA Repair; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism*; D008836:Micrococcal Nuclease; D011740:Pyrimidine Dimers / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D056565:Sirtuin 2 / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
chemical_list: D002843:Chromatin; D006657:Histones; D011740:Pyrimidine Dimers; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D008836:Micrococcal Nuclease; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2
references.citation: Mol Cell Biol. 2004 Dec;24(24):10857-67
references.pmid: 15572688
references.citation: Science. 1988 Jul 15;241(4863):317-22
references.pmid: 3291120
references.citation: Nature. 2000 Feb 17;403(6771):795-800
references.pmid: 10693811
references.citation: Nucleic Acids Res. 2001 Jul 1;29(13):E64-4
references.pmid: 11433040
references.citation: Mol Cell Biol. 2008 Apr;28(7):2380-90
references.pmid: 18212041
references.citation: Cell. 1999 Aug 6;98(3):285-94
references.pmid: 10458604
references.citation: Genes Dev. 1992 May;6(5):801-14
references.pmid: 1577274
references.citation: EMBO J. 1999 May 4;18(9):2538-50
references.pmid: 10228167
references.citation: Biochem Soc Trans. 2003 Feb;31(Pt 1):242-6
references.pmid: 12546694
references.citation: EMBO J. 2001 Apr 17;20(8):2004-14
references.pmid: 11296233
references.citation: Yeast. 1994 Dec;10(13):1793-808
references.pmid: 7747518
references.citation: Biochem Cell Biol. 2006 Aug;84(4):490-504
references.pmid: 16936822
references.citation: DNA Repair (Amst). 2009 Feb 1;8(2):146-52
references.pmid: 19041427
references.citation: DNA Repair (Amst). 2005 Jul 28;4(8):853-4
references.pmid: 15967734
references.citation: Genes Dev. 1993 Jul;7(7A):1146-59
references.pmid: 8319907
references.citation: Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7985-9
references.pmid: 8367452
references.citation: Eur J Biochem. 2004 Jun;271(12):2335-49
references.pmid: 15182349
references.citation: Mol Cell. 2001 Sep;8(3):489-98
references.pmid: 11583612
references.citation: Mol Cell Biol. 2002 Oct;22(19):6779-87
references.pmid: 12215535
references.citation: Mol Cell Biol. 1999 Jan;19(1):882-8
references.pmid: 9858611
references.citation: Mol Cell Biol. 1999 Jan;19(1):934-40
references.pmid: 9858617
references.citation: Mol Biol Cell. 2002 Jul;13(7):2207-22
references.pmid: 12134062
references.citation: Cell. 1990 Nov 16;63(4):751-62
references.pmid: 2225075
references.citation: Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12061-5
references.pmid: 7991584
references.citation: EMBO J. 1997 Aug 15;16(16):5046-56
references.pmid: 9305646
references.citation: EMBO J. 2005 Jun 15;24(12):2138-49
references.pmid: 15920479
references.citation: EMBO Rep. 2008 Jan;9(1):97-102
references.pmid: 18007656
references.citation: Cell. 1995 Mar 24;80(6):859-68
references.pmid: 7697716
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13153-9
references.pmid: 19666585
references.citation: Proc Natl Acad Sci U S A. 1990 Aug;87(16):6286-90
references.pmid: 2201024
references.citation: J Biol Chem. 2003 Sep 26;278(39):37471-9
references.pmid: 12882973
references.citation: Cell Cycle. 2005 Aug;4(8):1043-5
references.pmid: 16082210
references.citation: Genes Dev. 2006 Sep 15;20(18):2507-12
references.pmid: 16980580
references.citation: Nat Genet. 2002 Nov;32(3):370-7
references.pmid: 12410229
references.citation: Nucleic Acids Res. 2004 Mar 08;32(5):1617-26
references.pmid: 15007107
references.citation: J Biol Chem. 1991 Nov 25;266(33):22472-8
references.pmid: 1939267
references.citation: Nat Struct Mol Biol. 2006 Oct;13(10):902-7
references.pmid: 17013386
references.citation: J Biol Chem. 1995 Jun 2;270(22):12973-6
references.pmid: 7768886
references.citation: J Biol Chem. 1993 Apr 25;268(12):9098-104
references.pmid: 8386176
references.citation: J Biol Chem. 2002 Nov 22;277(47):44651-9
references.pmid: 12244104
references.citation: Nucleic Acids Res. 2009 Apr;37(5):1690-700
references.pmid: 19155276
references.citation: Mol Cell Biol. 1990 Oct;10(10):5257-70
references.pmid: 2204810
references.citation: J Biol Chem. 1982 Nov 25;257(22):13441-7
references.pmid: 7142158
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1609-14
references.pmid: 12571358
references.citation: DNA Repair (Amst). 2003 Apr 2;2(4):375-86
references.pmid: 12606119
references.citation: Genes Dev. 1997 Mar 15;11(6):748-60
references.pmid: 9087429
references.citation: Proc Natl Acad Sci U S A. 1978 Sep;75(9):4238-41
references.pmid: 279912
references.citation: Mol Cell Biol. 2002 Jun;22(12):4167-80
references.pmid: 12024030
references.citation: Mol Cell Biol. 2005 Jun;25(11):4514-28
references.pmid: 15899856
references.citation: Trends Biochem Sci. 2001 Nov;26(11):685-6
references.pmid: 11701328
references.citation: Proc Natl Acad Sci U S A. 2000 May 23;97(11):5807-11
references.pmid: 10811920
references.citation: Epigenetics Chromatin. 2009 Dec 02;2(1):18
references.pmid: 19954519
references.citation: Nat Genet. 2002 Nov;32(3):378-83
references.pmid: 12379856
references.citation: Genes Dev. 1999 Apr 1;13(7):768-85
references.pmid: 10197977
references.citation: Oncogene. 2007 Aug 13;26(37):5505-20
references.pmid: 17694090
references.citation: Annu Rev Biochem. 2003;72:481-516
references.pmid: 12676793
references.citation: Genes Dev. 1994 May 15;8(10):1133-46
references.pmid: 7926719
references.citation: Mutat Res. 2000 Jun 30;451(1-2):13-24
references.pmid: 10915862
references.citation: Mol Cell Biol. 2000 Nov;20(21):7991-8000
references.pmid: 11027269
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8650-5
references.pmid: 15939881
references.citation: Trends Cell Biol. 1992 Jan;2(1):10-4
references.pmid: 14731632