Heat shock protein DNAJA2 regulates transcription-coupled repair by triggering CSB degradation via chaperone-mediated autophagy.


Journal

Cell discovery
ISSN: 2056-5968
Titre abrégé: Cell Discov
Pays: England
ID NLM: 101661034

Informations de publication

Date de publication:
31 Oct 2023
Historique:
received: 19 07 2023
accepted: 01 09 2023
medline: 1 11 2023
pubmed: 1 11 2023
entrez: 1 11 2023
Statut: epublish

Résumé

Transcription-coupled nucleotide excision repair (TC-NER) is an important genome maintenance system that preferentially removes DNA lesions on the transcribed strand of actively transcribed genes, including non-coding genes. TC-NER involves lesion recognition by the initiation complex consisting of RNA polymerase II (Pol II) and Cockayne syndrome group B (CSB), followed by NER-catalyzed lesion removal. However, the efficient lesion removal requires the initiation complex to yield the right of way to the excision machinery, and how this occurs in a timely manner is unknown. Here we show that heat shock protein DNAJA2 facilitates the HSC70 chaperone-mediated autophagy (CMA) to degrade CSB during TC-NER. DNAJA2 interacts with and enables HSC70 to recognize sumoylated CSB. This triggers the removal of both CSB and Pol II from the lesion site in a manner dependent on lysosome receptor LAMP2A. Defects in DNAJA2, HSC70 or LAMP2A abolish CSB degradation and block TC-NER. Our findings discover DNAJA2-mediated CMA as a critical regulator of TC-NER, implicating the DNAJA2-HSC70-CMA axis factors in genome maintenance.

Identifiants

pubmed: 37907457
doi: 10.1038/s41421-023-00601-8
pii: 10.1038/s41421-023-00601-8
pmc: PMC10618452
doi:

Types de publication

Journal Article

Langues

eng

Pagination

107

Subventions

Organisme : Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas)
ID : RR160101

Informations de copyright

© 2023. The Author(s).

Références

Nat Genet. 2012 May;44(5):586-92
pubmed: 22466610
Cell Res. 2008 Jan;18(1):73-84
pubmed: 18166977
Nature. 2012 Sep 6;489(7414):101-8
pubmed: 22955620
Nat Cell Biol. 2022 Apr;24(4):483-496
pubmed: 35411088
Nat Rev Mol Cell Biol. 2018 Jun;19(6):365-381
pubmed: 29626215
Cell. 1995 Mar 24;80(6):859-68
pubmed: 7697716
Nat Genet. 2012 May;44(5):598-602
pubmed: 22466611
Nat Rev Mol Cell Biol. 2019 Nov;20(11):665-680
pubmed: 31253954
Science. 1994 Dec 23;266(5193):1957-8
pubmed: 7801121
DNA Repair (Amst). 2015 Dec;36:28-35
pubmed: 26422136
DNA Repair (Amst). 2018 Nov;71:56-68
pubmed: 30195642
Cell Death Dis. 2022 Feb 24;13(2):177
pubmed: 35210409
J Biol Chem. 2019 Mar 15;294(11):4247-4258
pubmed: 30670591
Cell. 2020 Mar 19;180(6):1228-1244.e24
pubmed: 32142649
Mech Ageing Dev. 2013 May-Jun;134(5-6):202-11
pubmed: 23422418
Nat Commun. 2015 Apr 16;6:6823
pubmed: 25880015
Nat Commun. 2023 Aug 28;14(1):5246
pubmed: 37640708
Prog Nucleic Acid Res Mol Biol. 2005;79:183-235
pubmed: 16096029
Mol Cell. 2005 Oct 28;20(2):187-98
pubmed: 16246722
Nat Rev Mol Cell Biol. 2014 Jul;15(7):465-81
pubmed: 24954209
J Cell Biol. 2010 May 3;189(3):425-43
pubmed: 20439996
Mol Cell. 2010 Jan 29;37(2):235-46
pubmed: 20122405
Nucleic Acids Res. 2020 Jan 10;48(1):231-248
pubmed: 31722399
J Biol Chem. 2018 Feb 16;293(7):2476-2486
pubmed: 29282293
Science. 2014 Jan 3;343(6166):84-87
pubmed: 24336571
Nat Commun. 2019 Jun 28;10(1):2885
pubmed: 31253769
J Biol Chem. 1975 Nov 25;250(22):8748-52
pubmed: 1184590
Cell. 2020 Mar 19;180(6):1245-1261.e21
pubmed: 32142654
Proc Natl Acad Sci U S A. 1986 Dec;83(23):8878-82
pubmed: 3466163
Cancer Sci. 2011 Oct;102(10):1840-7
pubmed: 21756275
DNA Repair (Amst). 2018 Nov;71:43-55
pubmed: 30174298
Cell Res. 2008 Jan;18(1):64-72
pubmed: 18166981
Nucleic Acids Res. 2018 Sep 6;46(15):7471-7479
pubmed: 30032309
Annu Rev Biochem. 1996;65:43-81
pubmed: 8811174
J Biol Chem. 2010 Jan 29;285(5):3319-29
pubmed: 19940115
J Biol Chem. 1996 Apr 5;271(14):8285-94
pubmed: 8626523
Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15300-5
pubmed: 21876155
Science. 1996 Apr 26;272(5261):557-60
pubmed: 8614807
J Biol Chem. 2016 Jan 15;291(3):1387-97
pubmed: 26620705
Nat Commun. 2018 Mar 12;9(1):1040
pubmed: 29531219
Nature. 2017 Nov 30;551(7682):653-657
pubmed: 29168508
J Dermatol Sci. 2002 Feb;28(2):144-51
pubmed: 11858953
Nat Commun. 2021 Feb 26;12(1):1342
pubmed: 33637760
Ann Dermatol. 2008 Dec;20(4):184-9
pubmed: 27303188
Nat Rev Mol Cell Biol. 2008 Dec;9(12):958-70
pubmed: 19023283
Nat Genet. 2012 May;44(5):593-7
pubmed: 22466612
DNA Repair (Amst). 2017 Apr;52:70-80
pubmed: 28237621
BMC Biochem. 2011 Jan 08;12:2
pubmed: 21214942
Genes Dev. 2006 Jun 1;20(11):1429-34
pubmed: 16751180
Nature. 1968 May 18;218(5142):652-6
pubmed: 5655953
Genes Dev. 2015 May 1;29(9):948-60
pubmed: 25934506
J Biol Chem. 1998 May 22;273(21):12887-92
pubmed: 9582319
Nat Rev Mol Cell Biol. 2019 Dec;20(12):766-784
pubmed: 31558824
Sci Rep. 2020 Mar 6;10(1):4176
pubmed: 32144307
J Biol Chem. 2016 Apr 1;291(14):7396-408
pubmed: 26826127

Auteurs

Yaping Huang (Y)

Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Liya Gu (L)

Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Guo-Min Li (GM)

Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA. Guo-Min.Li@UTSouthwestern.edu.
Chinese Institutes for Medical Research, Beijing, China. Guo-Min.Li@UTSouthwestern.edu.

Classifications MeSH