RNAPII-dependent ATM signaling at collisions with replication forks.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
24 08 2023
Historique:
received: 13 01 2023
accepted: 16 08 2023
medline: 28 8 2023
pubmed: 25 8 2023
entrez: 24 8 2023
Statut: epublish

Résumé

Deregulation of RNA Polymerase II (RNAPII) by oncogenic signaling leads to collisions of RNAPII with DNA synthesis machinery (transcription-replication conflicts, TRCs). TRCs can result in DNA damage and are thought to underlie genomic instability in tumor cells. Here we provide evidence that elongating RNAPII nucleates activation of the ATM kinase at TRCs to stimulate DNA repair. We show the ATPase WRNIP1 associates with RNAPII and limits ATM activation during unperturbed cell cycle. WRNIP1 binding to elongating RNAPII requires catalytic activity of the ubiquitin ligase HUWE1. Mutation of HUWE1 induces TRCs, promotes WRNIP1 dissociation from RNAPII and binding to the replisome, stimulating ATM recruitment and activation at RNAPII. TRCs and translocation of WRNIP1 are rapidly induced in response to hydroxyurea treatment to activate ATM and facilitate subsequent DNA repair. We propose that TRCs can provide a controlled mechanism for stalling of replication forks and ATM activation, instrumental in cellular response to replicative stress.

Identifiants

pubmed: 37620345
doi: 10.1038/s41467-023-40924-4
pii: 10.1038/s41467-023-40924-4
pmc: PMC10449895
doi:

Substances chimiques

RNA Polymerase II EC 2.7.7.-
Hydrolases EC 3.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5147

Informations de copyright

© 2023. Springer Nature Limited.

Références

Nucleic Acids Res. 2009 May;37(8):2645-57
pubmed: 19270065
Redox Biol. 2014 Jan 09;2:457-65
pubmed: 24624335
J Biomed Sci. 2018 Sep 4;25(1):67
pubmed: 30176860
Cell Rep. 2019 Aug 20;28(8):2182-2193.e6
pubmed: 31433991
Nat Commun. 2016 Oct 11;7:13087
pubmed: 27725641
Genes Dev. 2019 Aug 1;33(15-16):1008-1026
pubmed: 31123061
Cell. 2016 Dec 1;167(6):1455-1467
pubmed: 27912056
DNA Repair (Amst). 2006 May 10;5(5):575-90
pubmed: 16567133
Cell Cycle. 2017 Mar 19;16(6):515-521
pubmed: 28118071
Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):E1148-E1157
pubmed: 28137882
Mol Cell. 2021 Feb 18;81(4):830-844.e13
pubmed: 33453168
Angew Chem Int Ed Engl. 2015 Feb 2;54(6):1859-63
pubmed: 25504624
Mol Cell. 2012 Mar 30;45(6):710-8
pubmed: 22464441
Annu Rev Biochem. 2018 Jun 20;87:263-294
pubmed: 29709199
DNA Repair (Amst). 2009 Apr 5;8(4):461-9
pubmed: 19217833
EMBO Rep. 2021 Apr 7;22(4):e51078
pubmed: 33779035
J Cell Sci. 2015 Dec 1;128(23):4255-62
pubmed: 26567218
EMBO Rep. 2016 Jun;17(6):874-86
pubmed: 27146073
Nat Struct Mol Biol. 2019 Jan;26(1):58-66
pubmed: 30598553
Methods Mol Biol. 2017;1558:41-55
pubmed: 28150232
Nucleic Acids Res. 2002 Jan 1;30(1):207-10
pubmed: 11752295
NAR Cancer. 2022 Apr 08;4(2):zcac013
pubmed: 35399185
Cell Rep. 2021 Jan 5;34(1):108565
pubmed: 33406426
DNA Repair (Amst). 2022 Jan;109:103211
pubmed: 34883263
Genes Dev. 2004 Dec 15;18(24):3094-105
pubmed: 15601823
Nat Commun. 2018 Apr 23;9(1):1590
pubmed: 29686321
Cancer Sci. 2020 May;111(5):1443-1451
pubmed: 32232911
Oncogenesis. 2022 Jun 18;11(1):33
pubmed: 35717336
J Biol Chem. 2008 Dec 12;283(50):35173-85
pubmed: 18842586
Cell Mol Life Sci. 2021 Jul;78(14):5543-5567
pubmed: 34146121
Nat Struct Mol Biol. 2011 Nov 27;18(12):1331-1335
pubmed: 22120667
Methods. 2016 Oct 1;108:92-8
pubmed: 27102626
Cell. 2019 Oct 17;179(3):604-618
pubmed: 31607512
Mol Biol Cell. 2010 Mar 1;21(5):739-52
pubmed: 20053681
J Mol Biol. 2021 Jul 9;433(14):166979
pubmed: 33811920
J Biol Chem. 2003 Sep 12;278(37):34739-42
pubmed: 12876294
Nat Commun. 2022 Jan 14;13(1):316
pubmed: 35031618
Nat Rev Cancer. 2015 May;15(5):276-89
pubmed: 25907220
Nucleic Acids Res. 2012 Jan;40(1):245-57
pubmed: 21911365
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Genome Biol. 2021 Jun 9;22(1):176
pubmed: 34108027
Nat Cell Biol. 2017 Dec;19(12):1400-1411
pubmed: 29180822
Cell. 2014 Nov 20;159(5):1126-1139
pubmed: 25416950
J Biol Chem. 2001 Dec 21;276(51):47759-62
pubmed: 11673449
J Proteome Res. 2011 Apr 1;10(4):1794-805
pubmed: 21254760
Sci Adv. 2021 May 21;7(21):
pubmed: 34020942
EMBO J. 2016 Jul 1;35(13):1437-51
pubmed: 27242363
Nat Rev Mol Cell Biol. 2013 Apr;14(4):197-210
pubmed: 23486281
Genome Biol. 2014;15(12):554
pubmed: 25476604
Nucleic Acids Res. 2019 Oct 10;47(18):9467-9479
pubmed: 31396623
EMBO J. 2015 Jan 13;34(2):236-50
pubmed: 25452497
Nucleic Acids Res. 2015 Mar 31;43(6):e35
pubmed: 25223787
BMC Mol Biol. 2010 Mar 06;11:18
pubmed: 20205745
iScience. 2019 Nov 22;21:31-41
pubmed: 31654852
Biophys Rev. 2016 Nov;8(Suppl 1):75-87
pubmed: 28275417
Nat Protoc. 2007;2(8):1896-906
pubmed: 17703201
Cancer Res. 2004 Apr 1;64(7):2390-6
pubmed: 15059890
EMBO J. 2015 Jun 3;34(11):1554-71
pubmed: 25896507
Nat Protoc. 2017 Apr;12(4):828-863
pubmed: 28333914
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Sci Rep. 2017 Nov 10;7(1):15353
pubmed: 29127375
Cancer Discov. 2018 May;8(5):537-555
pubmed: 29653955
Nat Commun. 2021 Jul 5;12(1):4126
pubmed: 34226554
Nat Protoc. 2016 Dec;11(12):2301-2319
pubmed: 27809316
Genes Dev. 2016 Feb 1;30(3):337-54
pubmed: 26798134
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Mol Cell. 2019 Feb 7;73(3):398-411
pubmed: 30735654
Nature. 2015 Jul 2;523(7558):53-8
pubmed: 26106861
Genes Dev. 2003 Dec 15;17(24):3017-22
pubmed: 14681210
Oncogene. 2016 Jul 28;35(30):4009-19
pubmed: 26549024
Cell Cycle. 2009 Feb 1;8(3):498-504
pubmed: 19177017
Nat Methods. 2016 Oct;13(10):855-7
pubmed: 27525976
Nat Commun. 2018 Jul 13;9(1):2706
pubmed: 30006506
Cold Spring Harb Perspect Biol. 2013 Sep 01;5(9):
pubmed: 24003211
Genes Dev. 2014 Aug 15;28(16):1800-14
pubmed: 25128497
Nat Chem Biol. 2011 Mar;7(3):182-8
pubmed: 21278739
Nucleic Acids Res. 2020 Jul 2;48(W1):W488-W493
pubmed: 32246720
Elife. 2019 Jun 24;8:
pubmed: 31232687
DNA Repair (Amst). 2017 Sep;57:29-34
pubmed: 28648892
Transcription. 2011 May;2(3):103-108
pubmed: 21922053
Nucleic Acids Res. 2022 Jan 7;50(D1):D543-D552
pubmed: 34723319
Nat Methods. 2016 Sep;13(9):731-40
pubmed: 27348712
Nature. 2018 Mar 1;555(7694):112-116
pubmed: 29466339
Bio Protoc. 2017 Nov 5;7(21):
pubmed: 29170752
EMBO Rep. 2010 Nov;11(11):876-82
pubmed: 20930849
Cell. 2005 Nov 4;123(3):409-21
pubmed: 16269333
EMBO Mol Med. 2014 Sep 24;6(12):1525-41
pubmed: 25253726
RNA. 2003 Apr;9(4):493-501
pubmed: 12649500
Protein Sci. 2021 Jan;30(1):187-200
pubmed: 33070389
Cell. 2017 Aug 10;170(4):774-786.e19
pubmed: 28802045
Mol Cell. 2010 Feb 26;37(4):492-502
pubmed: 20188668
EMBO J. 2006 Apr 19;25(8):1764-74
pubmed: 16601701

Auteurs

Elias Einig (E)

Department of Medical Oncology and Pulmonology, University Hospital Tübingen, Otfried-Mueller-Str 14, 72076, Tübingen, Germany.

Chao Jin (C)

Department of Medical Oncology and Pulmonology, University Hospital Tübingen, Otfried-Mueller-Str 14, 72076, Tübingen, Germany.

Valentina Andrioletti (V)

Department of Medical Oncology and Pulmonology, University Hospital Tübingen, Otfried-Mueller-Str 14, 72076, Tübingen, Germany.
enGenome S.R.L., Via Fratelli Cuzio 42, 27100, Pavia, Italy.

Boris Macek (B)

Interfaculty Institute of Cell Biology, Eberhard Karls University of Tübingen, Auf d. Morgenstelle 15, 72076, Tübingen, Germany.

Nikita Popov (N)

Department of Medical Oncology and Pulmonology, University Hospital Tübingen, Otfried-Mueller-Str 14, 72076, Tübingen, Germany. nikita.popov@med.uni-tuebingen.de.

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