Endogenous oxidized DNA bases and APE1 regulate the formation of G-quadruplex structures in the genome.
A549 Cells
Acetylation
DNA Damage
DNA Repair
/ physiology
DNA-(Apurinic or Apyrimidinic Site) Lyase
/ genetics
G-Quadruplexes
Gene Expression
Genes, myc
Genome, Human
Guanine
/ chemistry
HCT116 Cells
Humans
Oxidation-Reduction
Oxidative Stress
/ genetics
Promoter Regions, Genetic
Proto-Oncogene Proteins p21(ras)
/ genetics
Transcription Factors
/ genetics
8-oxoguanine
APE1
G-quadruplex structures
base excision repair
endogenous damage
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
26 05 2020
26 05 2020
Historique:
pubmed:
15
5
2020
medline:
25
8
2020
entrez:
15
5
2020
Statut:
ppublish
Résumé
Formation of G-quadruplex (G4) DNA structures in key regulatory regions in the genome has emerged as a secondary structure-based epigenetic mechanism for regulating multiple biological processes including transcription, replication, and telomere maintenance. G4 formation (folding), stabilization, and unfolding must be regulated to coordinate G4-mediated biological functions; however, how cells regulate the spatiotemporal formation of G4 structures in the genome is largely unknown. Here, we demonstrate that endogenous oxidized guanine bases in G4 sequences and the subsequent activation of the base excision repair (BER) pathway drive the spatiotemporal formation of G4 structures in the genome. Genome-wide mapping of occurrence of Apurinic/apyrimidinic (AP) site damage, binding of BER proteins, and G4 structures revealed that oxidized base-derived AP site damage and binding of OGG1 and APE1 are predominant in G4 sequences. Loss of APE1 abrogated G4 structure formation in cells, which suggests an essential role of APE1 in regulating the formation of G4 structures in the genome. Binding of APE1 to G4 sequences promotes G4 folding, and acetylation of APE1, which enhances its residence time, stabilizes G4 structures in cells. APE1 subsequently facilitates transcription factor loading to the promoter, providing mechanistic insight into the role of APE1 in G4-mediated gene expression. Our study unravels a role of endogenous oxidized DNA bases and APE1 in controlling the formation of higher-order DNA secondary structures to regulate transcription beyond its well-established role in safeguarding the genomic integrity.
Identifiants
pubmed: 32404420
pii: 1912355117
doi: 10.1073/pnas.1912355117
pmc: PMC7260947
doi:
Substances chimiques
KRAS protein, human
0
Transcription Factors
0
Guanine
5Z93L87A1R
Proto-Oncogene Proteins p21(ras)
EC 3.6.5.2
APEX1 protein, human
EC 4.2.99.18
DNA-(Apurinic or Apyrimidinic Site) Lyase
EC 4.2.99.18
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11409-11420Subventions
Organisme : NCI NIH HHS
ID : F99 CA223064
Pays : United States
Organisme : NCI NIH HHS
ID : K00 CA223064
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA148941
Pays : United States
Organisme : NCI NIH HHS
ID : R03 CA235214
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA036727
Pays : United States
Informations de copyright
Copyright © 2020 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
Références
J Biol Chem. 2019 Mar 29;294(13):5198-5207
pubmed: 30705092
ACS Cent Sci. 2015 Aug 26;1(5):226-233
pubmed: 26405692
Nucleic Acids Res. 2015 Aug 18;43(14):7171
pubmed: 26117536
J Biol Chem. 2004 Dec 17;279(51):53465-74
pubmed: 15385537
DNA Repair (Amst). 2007 Apr 1;6(4):544-59
pubmed: 17112792
Biochemistry. 2012 Jul 3;51(26):5257-68
pubmed: 22667821
Nucleic Acids Res. 2018 Jan 25;46(2):661-676
pubmed: 29165690
Biopolymers. 2018 Aug;109(8):e23098
pubmed: 29322505
J Mol Biol. 2011 Sep 2;411(5):960-71
pubmed: 21762700
Prog Biophys Mol Biol. 2019 Oct;147:47-61
pubmed: 30880007
Nucleic Acids Res. 2016 Nov 16;44(20):e153
pubmed: 27484474
Nucleic Acids Res. 2014 Jul;42(12):7708-19
pubmed: 24848015
Curr Mol Pharmacol. 2012 Jan;5(1):36-53
pubmed: 22122463
Nat Rev Mol Cell Biol. 2017 May;18(5):279-284
pubmed: 28225080
Nature. 2000 Jan 27;403(6768):451-6
pubmed: 10667800
Biochem Soc Trans. 2017 Oct 15;45(5):1173-1182
pubmed: 28939694
Nucleic Acids Res. 2010 Apr;38(6):2069-80
pubmed: 20026588
Nucleic Acids Res. 2008 Oct;36(17):5482-515
pubmed: 18718931
Proc Natl Acad Sci U S A. 2013 Oct 29;110(44):17844-9
pubmed: 24127576
Antioxid Redox Signal. 2009 Mar;11(3):601-20
pubmed: 18976116
Antioxid Redox Signal. 2014 Feb 1;20(4):678-707
pubmed: 23834463
Genome Res. 2017 Oct;27(10):1674-1684
pubmed: 28912372
J Mol Biol. 2003 May 30;329(2):311-22
pubmed: 12758078
Int J Radiat Biol. 2014 Jun;90(6):423-32
pubmed: 24369822
Mol Cell Biol. 2017 Mar 1;37(6):
pubmed: 27994014
Nat Rev Genet. 2012 Nov;13(11):770-80
pubmed: 23032257
Science. 2008 Jan 11;319(5860):202-6
pubmed: 18187655
Nat Commun. 2019 Feb 26;10(1):943
pubmed: 30808951
Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11593-8
pubmed: 12195017
Free Radic Biol Med. 2012 Jul 1;53(1):51-9
pubmed: 22583700
Oxid Med Cell Longev. 2017;2017:2597581
pubmed: 28770020
Nucleic Acids Res. 2006;34(19):5402-15
pubmed: 17012276
Nucleic Acids Res. 2010 Jan;38(3):832-45
pubmed: 19934257
Antioxid Redox Signal. 2009 Mar;11(3):621-38
pubmed: 18715144
Nat Genet. 2016 Oct;48(10):1267-72
pubmed: 27618450
Proc Natl Acad Sci U S A. 2017 Mar 14;114(11):2788-2790
pubmed: 28265096
Mol Endocrinol. 2010 Feb;24(2):391-401
pubmed: 20032196
Free Radic Biol Med. 2015 Apr;81:107-18
pubmed: 25614460
Nat Struct Biol. 2000 Mar;7(3):176-8
pubmed: 10700268
Org Biomol Chem. 2017 Oct 11;15(39):8341-8353
pubmed: 28936535
Genes Cancer. 2010 Jun;1(6):641-649
pubmed: 21113409
J Biol Chem. 1998 Nov 13;273(46):30352-9
pubmed: 9804798
J Biol Chem. 2009 Sep 25;284(39):26402-10
pubmed: 19640839
Mol Cell Biol. 2008 Dec;28(23):7066-80
pubmed: 18809583
Am J Physiol Lung Cell Mol Physiol. 2015 Dec 1;309(11):L1367-75
pubmed: 26432868
Oncotarget. 2016 Nov 15;7(46):75197-75209
pubmed: 27655688
Nucleic Acids Res. 2009 Sep;37(17):5749-56
pubmed: 19617376
Proteins. 2018 Apr;86(4):439-453
pubmed: 29344998
J Am Chem Soc. 2014 Feb 5;136(5):1750-3
pubmed: 24450880
Mech Ageing Dev. 2007 Nov-Dec;128(11-12):637-49
pubmed: 18006041
Nat Protoc. 2018 Mar;13(3):551-564
pubmed: 29470465
Nat Struct Mol Biol. 2016 Dec;23(12):1092-1100
pubmed: 27820808
Bioinformatics. 2017 Oct 15;33(20):3158-3165
pubmed: 29028265
J Immunol. 2014 Mar 1;192(5):2384-94
pubmed: 24489103
J Biol Chem. 2016 Dec 2;291(49):25553-25566
pubmed: 27756845
Proc Natl Acad Sci U S A. 2017 Mar 7;114(10):2604-2609
pubmed: 28143930
Biochimie. 2017 Apr;135:54-62
pubmed: 28109719
Nucleic Acids Res. 2015 Oct 15;43(18):8627-37
pubmed: 26350216
Transcription. 2011 May;2(3):103-108
pubmed: 21922053
EMBO Rep. 2015 Aug;16(8):910-22
pubmed: 26150098
Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W676-82
pubmed: 16845096
Mol Cell Biol. 2006 Mar;26(5):1654-65
pubmed: 16478987
Biochemistry. 1992 Apr 14;31(14):3703-8
pubmed: 1567824
Proc Natl Acad Sci U S A. 1962 Dec 15;48:2013-8
pubmed: 13947099
Genome Biol. 2018 Dec 7;19(1):215
pubmed: 30526646
J Biol Chem. 2013 Mar 22;288(12):8445-55
pubmed: 23355472
EMBO J. 2003 Dec 1;22(23):6299-309
pubmed: 14633989
Nucleic Acids Res. 2001 Jan 15;29(2):430-8
pubmed: 11139613
Oncogene. 2011 Jan 27;30(4):482-93
pubmed: 20856196
Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):686-91
pubmed: 10639140
Nucleic Acids Res. 2019 May 7;47(8):3862-3874
pubmed: 30892612
Nature. 1993 Apr 22;362(6422):709-15
pubmed: 8469282
Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5739-43
pubmed: 15824325