Trypanosoma brucei ATR Links DNA Damage Signaling during Antigenic Variation with Regulation of RNA Polymerase I-Transcribed Surface Antigens.
Alleles
Antigenic Variation
Antigens, Surface
/ genetics
Ataxia Telangiectasia Mutated Proteins
/ metabolism
Cell Nucleus
/ pathology
Cell Proliferation
Cell Survival
DNA Damage
Gene Expression Regulation
Genome
Models, Biological
Protein Transport
Protozoan Proteins
/ metabolism
RNA Interference
RNA Polymerase I
/ metabolism
Transcription, Genetic
Trypanosoma brucei brucei
/ cytology
ATR
DNA damage signaling
DNA replication stress
RNA polymerase I
Trypanosoma brucei
antigenic variation
immune evasion
monoallelic expression
protein kinase
variant surface glycoprotein
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
21 01 2020
21 01 2020
Historique:
received:
13
12
2018
revised:
19
08
2019
accepted:
13
12
2019
entrez:
23
1
2020
pubmed:
23
1
2020
medline:
18
3
2021
Statut:
ppublish
Résumé
Trypanosoma brucei evades mammalian immunity by using recombination to switch its surface-expressed variant surface glycoprotein (VSG), while ensuring that only one of many subtelomeric multigene VSG expression sites are transcribed at a time. DNA repair activities have been implicated in the catalysis of VSG switching by recombination, not transcriptional control. How VSG switching is signaled to guide the appropriate reaction or to integrate switching into parasite growth is unknown. Here, we show that the loss of ATR, a DNA damage-signaling protein kinase, is lethal, causing nuclear genome instability and increased VSG switching through VSG-localized damage. Furthermore, ATR loss leads to the increased transcription of silent VSG expression sites and expression of mixed VSGs on the cell surface, effects that are associated with the altered localization of RNA polymerase I and VEX1. This work shows that ATR acts in antigenic variation both through DNA damage signaling and surface antigen expression control.
Identifiants
pubmed: 31968257
pii: S2211-1247(19)31706-1
doi: 10.1016/j.celrep.2019.12.049
pmc: PMC6988115
pii:
doi:
Substances chimiques
Antigens, Surface
0
Protozoan Proteins
0
Ataxia Telangiectasia Mutated Proteins
EC 2.7.11.1
RNA Polymerase I
EC 2.7.7.6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
836-851.e5Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M028909/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 104111
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/K006495/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/N016165/1
Pays : United Kingdom
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
Références
Genome Res. 2007 Sep;17(9):1344-52
pubmed: 17652423
Cell Microbiol. 2013 Dec;15(12):1984-93
pubmed: 24047558
EMBO J. 2007 May 2;26(9):2400-10
pubmed: 17431399
Nat Protoc. 2016 Sep;11(9):1650-67
pubmed: 27560171
Mol Microbiol. 2013 Dec;90(5):1074-87
pubmed: 24118609
Nucleic Acids Res. 2016 Jan 29;44(2):538-44
pubmed: 26615196
Mol Microbiol. 2008 Jun;68(5):1237-51
pubmed: 18430140
Trends Biochem Sci. 2015 May;40(5):275-85
pubmed: 25845889
Microbiol Mol Biol Rev. 2014 Mar;78(1):40-73
pubmed: 24600040
Mol Biochem Parasitol. 2005 Dec;144(2):142-8
pubmed: 16182389
J Cell Sci. 2009 Nov 15;122(Pt 22):4070-80
pubmed: 19843584
Microbiol Spectr. 2015 Apr;3(2):MDNA3-0016-2014
pubmed: 26104717
PLoS Biol. 2012;10(3):e1001287
pubmed: 22479148
Nucleic Acids Res. 2015 Mar 11;43(5):2489-98
pubmed: 25712102
Trends Parasitol. 2016 Aug;32(8):599-607
pubmed: 27167665
EMBO Rep. 2006 Jan;7(1):93-9
pubmed: 16311518
Mol Biochem Parasitol. 2016 Sep - Oct;209(1-2):104-113
pubmed: 27475118
Mol Microbiol. 2013 Jan;87(1):196-210
pubmed: 23216794
Nucleic Acids Res. 2019 Jan 25;47(2):634-647
pubmed: 30407533
Proc Natl Acad Sci U S A. 2015 May 26;112(21):E2803-12
pubmed: 25964327
Cell. 2002 Dec 13;111(6):779-89
pubmed: 12526805
PLoS One. 2011;6(9):e25313
pubmed: 21980422
Nucleic Acids Res. 2014 Nov 10;42(20):12899-911
pubmed: 25313155
Mol Cell Biol. 1998 Jan;18(1):198-205
pubmed: 9418867
PLoS Genet. 2018 Dec 13;14(12):e1007729
pubmed: 30543624
Science. 2002 Jul 26;297(5581):602-6
pubmed: 12142538
EMBO J. 1999 Sep 1;18(17):4846-55
pubmed: 10469662
Nucleic Acids Res. 2007;35(3):872-80
pubmed: 17251198
Science. 2017 Dec 1;358(6367):1206-1209
pubmed: 29191911
Nucleic Acids Res. 2012 Nov 1;40(20):10150-60
pubmed: 22941664
PLoS One. 2016 Jun 03;11(6):e0156746
pubmed: 27258069
Nucleic Acids Res. 2018 Jul 2;46(W1):W537-W544
pubmed: 29790989
Cell Microbiol. 2013 May;15(5):718-26
pubmed: 23351305
Mol Biochem Parasitol. 2011 May;177(1):65-9
pubmed: 21291918
Genes Dev. 2000 Feb 15;14(4):397-402
pubmed: 10691732
Bioinformatics. 2006 Jul 1;22(13):1600-7
pubmed: 16606683
Curr Biol. 2017 Jan 9;27(1):R33-R35
pubmed: 28073021
Genome Biol. 2014;15(12):550
pubmed: 25516281
BMC Genomics. 2016 Oct 18;17(1):806
pubmed: 27756224
Mol Biochem Parasitol. 2008 Sep;161(1):76-9
pubmed: 18588918
Plant Cell. 2004 May;16(5):1091-104
pubmed: 15075397
PLoS Genet. 2009 Aug;5(8):e1000622
pubmed: 19714219
PLoS Genet. 2015 Aug 11;11(8):e1005438
pubmed: 26263206
Nucleic Acids Res. 2013 Mar 1;41(5):2981-92
pubmed: 23361461
Nat Cell Biol. 2004 Jul;6(7):648-55
pubmed: 15220931
J Biol Chem. 2004 Apr 2;279(14):13363-74
pubmed: 14726511
DNA Repair (Amst). 2009 Sep 2;8(9):1004-8
pubmed: 19464237
Mol Biochem Parasitol. 1994 Jan;63(1):143-51
pubmed: 8183314
Trends Parasitol. 2014 May;30(5):251-8
pubmed: 24731931
Mol Biochem Parasitol. 2002 Jul;122(2):131-40
pubmed: 12106867
PLoS Pathog. 2013 Mar;9(3):e1003260
pubmed: 23555264
DNA Repair (Amst). 2019 Jan;73:78-90
pubmed: 30470509
Nat Rev Mol Cell Biol. 2017 Oct;18(10):622-636
pubmed: 28811666
Elife. 2014 May 20;3:e02324
pubmed: 24844706
Mol Cell. 2015 Sep 17;59(6):998-1010
pubmed: 26365379
Nature. 2007 Aug 30;448(7157):1068-71
pubmed: 17687332
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Cell Rep. 2012 Jul 26;2(1):185-97
pubmed: 22840408
Cell Tissue Res. 2014 Jun;356(3):457-66
pubmed: 24781148
Nat Protoc. 2008;3(6):1101-8
pubmed: 18546601
PLoS Pathog. 2012;8(8):e1002900
pubmed: 22952449
Cell. 2012 Jun 8;149(6):1221-32
pubmed: 22682245
Proc Natl Acad Sci U S A. 2011 Feb 22;108(8):3108-15
pubmed: 21292986
Nat Struct Mol Biol. 2011 Nov 20;18(12):1408-13
pubmed: 22101932
Annu Rev Genet. 2016 Nov 23;50:155-173
pubmed: 27617969
Curr Genet. 2017 Jun;63(3):441-449
pubmed: 27822899
Nucleic Acids Res. 2005 Dec 02;33(21):6906-19
pubmed: 16326865
Mol Microbiol. 2016 Sep;101(6):1054-68
pubmed: 27301589
J Cell Biol. 2009 Jul 27;186(2):243-54
pubmed: 19635842
BMC Genomics. 2005 Sep 15;6:127
pubmed: 16164760
Sci Rep. 2018 Mar 29;8(1):5405
pubmed: 29599445
Mol Microbiol. 2010 Oct;78(2):459-74
pubmed: 20879999
PLoS Pathog. 2014 Jan;10(1):e1003886
pubmed: 24453978
Stat Appl Genet Mol Biol. 2012 Mar 31;11(3):Article 9
pubmed: 22499706
Nucleic Acids Res. 2016 Dec 15;44(22):10554-10570
pubmed: 27625397
mBio. 2019 Jul 9;10(4):
pubmed: 31289179
Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):7225-30
pubmed: 27226299
Mol Biochem Parasitol. 2012 May;183(1):78-83
pubmed: 22353557
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Mol Microbiol. 2011 Jul;81(2):434-56
pubmed: 21615552
Nature. 2009 May 14;459(7244):278-81
pubmed: 19369939
Nucleic Acids Res. 2013 Jan;41(2):943-60
pubmed: 23222131
PLoS Pathog. 2010 Jul 08;6(7):e1000992
pubmed: 20628569
Science. 2005 Jul 15;309(5733):416-22
pubmed: 16020726
PLoS Pathog. 2014 Dec 04;10(12):e1004545
pubmed: 25474309
Cell Res. 2014 Jul;24(7):870-85
pubmed: 24810301
Cell. 2013 Jan 31;152(3):620-32
pubmed: 23352430
Biochimie. 2008 Jan;90(1):93-107
pubmed: 17868970
Sci Rep. 2017 Jul 21;7(1):6156
pubmed: 28733613
PLoS One. 2008;3(10):e3527
pubmed: 18953401
PLoS Biol. 2008 Jul 1;6(7):e161
pubmed: 18597556
Mol Biochem Parasitol. 1998 Sep 1;95(1):97-109
pubmed: 9763292
Mol Biochem Parasitol. 1999 Oct 15;103(2):141-54
pubmed: 10551359
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W187-91
pubmed: 24799436
PLoS Negl Trop Dis. 2017 Mar 6;11(3):e0005432
pubmed: 28263991
Cell Rep. 2015 Nov 24;13(8):1633-46
pubmed: 26586433
Nucleic Acids Res. 2019 Sep 26;47(17):9180-9197
pubmed: 31350892
Nat Methods. 2015 Apr;12(4):357-60
pubmed: 25751142
Proc Natl Acad Sci U S A. 2011 May 24;108(21):8663-7
pubmed: 21555580
Elife. 2016 May 26;5:
pubmed: 27228154
DNA Repair (Amst). 2016 Aug;44:143-150
pubmed: 27283761
Cold Spring Harb Perspect Biol. 2013 Aug 01;5(8):a012724
pubmed: 23813586
PLoS Pathog. 2018 Nov 15;14(11):e1007321
pubmed: 30440029
Nat Rev Mol Cell Biol. 2017 Mar;18(3):175-186
pubmed: 28096526
Science. 2015 Mar 27;347(6229):1470-3
pubmed: 25814582
Gene. 2015 Feb 1;556(1):68-73
pubmed: 25261847
PLoS Pathog. 2017 Jul 24;13(7):e1006477
pubmed: 28742144
Nucleic Acids Res. 2008 May;36(8):2608-18
pubmed: 18334531
Nature. 2001 Dec 13;414(6865):759-63
pubmed: 11742402
Nat Commun. 2019 Jul 9;10(1):3023
pubmed: 31289266
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Nucleic Acids Res. 2005 Aug 09;33(14):4536-43
pubmed: 16091631
Acta Trop. 1979 Sep;36(3):289-92
pubmed: 43092
Eur J Cell Biol. 1994 Jun;64(1):78-87
pubmed: 7957316
Cell Struct Funct. 2015;40(1):43-50
pubmed: 25748360
PLoS Pathog. 2013;9(7):e1003502
pubmed: 23853603
Nucleic Acids Res. 2016 Apr 20;44(7):3131-46
pubmed: 26673706
Genes Dev. 1999 Nov 1;13(21):2875-88
pubmed: 10557214
Cell. 2017 Aug 10;170(4):774-786.e19
pubmed: 28802045
Nat Cell Biol. 2014 Jan;16(1):2-9
pubmed: 24366029
Nucleic Acids Res. 2017 Jun 2;45(10):5785-5796
pubmed: 28334836
PLoS Pathog. 2012;8(11):e1003010
pubmed: 23133390
Mol Biochem Parasitol. 2014 Jun;195(1):59-73
pubmed: 24992042
Cell. 2009 Apr 3;137(1):99-109
pubmed: 19345190
Trends Parasitol. 2015 Aug;31(8):346-9
pubmed: 25999027
Nucleic Acids Res. 2018 Dec 14;46(22):11835-11846
pubmed: 30380080
Mol Cell. 2015 Apr 16;58(2):323-38
pubmed: 25843623
PLoS Negl Trop Dis. 2019 Apr 3;13(4):e0007262
pubmed: 30943202
Nature. 2018 Nov;563(7729):121-125
pubmed: 30333624