Poly(Adp-ribose) binding and macroh2a mediate recruitment and functions of kdm5a at dna lesions
Kumbhar, Ramhari (University of Texas at Austin)
Sanchez, Anthony (University of Texas at Austin)
Perren, Jullian (University of Texas at Austin)
Gong, Fade (Baylor College of Medicine)
Corujo, David (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Medina, Frank (University of Texas at Austin)
Devanathan, Sravan K. (University of Texas at Austin)
Xhemalce, Blerta (University of Texas at Austin)
Matouschek, Andreas (University of Texas at Austin)
Buschbeck, Marcus (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Buck-Koehntop, Bethany A. (University of Utah)
Miller, Kyle M. (University of Texas at Austin)
Universitat Autònoma de Barcelona
Date: |
2021 |
Abstract: |
The histone demethylase KDM5A erases histone H3 lysine 4 methylation, which is involved in transcription and DNA damage responses (DDRs). While DDR functions of KDM5A have been identified, how KDM5A recognizes DNA lesion sites within chromatin is unknown. Here, we identify two factors that act upstream of KDM5A to promote its association with DNA damage sites. We have identified a noncanonical poly(ADP-ribose) (PAR)-binding region unique to KDM5A. Loss of the PARbinding region or treatment with PAR polymerase (PARP) inhibitors (PARPi's) blocks KDM5A-PAR interactions and DNA repair functions of KDM5A. The histone variant macroH2A1. 2 is also specifically required for KDM5A recruitment and function at DNA damage sites, including homology-directed repair of DNA double-strand breaks and repression of transcription at DNA breaks. Overall, this work reveals the importance of PAR binding and macroH2A1. 2 in KDM5A recognition of DNA lesion sites that drive transcriptional and repair activities at DNA breaks within chromatin that are essential for maintaining genome integrity. |
Grants: |
Ministerio de Economía y Competitividad PIE16/00011 Agencia Estatal de Investigación RTI2018-094005-B-I00
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Rights: |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra, i la creació d'obres derivades, sempre que no sigui amb finalitats comercials i que es distribueixin sota la mateixa llicència que regula l'obra original. Cal que es reconegui l'autoria de l'obra original. |
Language: |
Anglès |
Document: |
Article ; recerca ; Versió publicada |
Subject: |
Chromatin ;
DNA ;
DNA Breaks, Double-Stranded ;
DNA Damage ;
Histones ;
Humans ;
Poly Adenosine Diphosphate Ribose ;
Poly(ADP-ribose) Polymerases ;
Recombinational DNA Repair ;
Retinoblastoma-Binding Protein 2 |
Published in: |
The journal of cell biology, Vol. 220 Núm. 7 (2021) , p. e202006149, ISSN 1540-8140 |
DOI: 10.1083/jcb.202006149
PMID: 34003252
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Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) >
Josep Carreras Leukaemia Research Institute Articles >
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Published articles
Record created 2023-01-17, last modified 2024-05-02