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Non-canonical reader modules of BAZ1A promote recovery from DNA damage
- Source :
- Nature Communications, Nature Communications, Vol 8, Iss 1, Pp 1-15 (2017)
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Members of the ISWI family of chromatin remodelers mobilize nucleosomes to control DNA accessibility and, in some cases, are required for recovery from DNA damage. However, it remains poorly understood how the non-catalytic ISWI subunits BAZ1A and BAZ1B might contact chromatin to direct the ATPase SMARCA5. Here, we find that the plant homeodomain of BAZ1A, but not that of BAZ1B, has the unusual function of binding DNA. Furthermore, the BAZ1A bromodomain has a non-canonical gatekeeper residue and binds relatively weakly to acetylated histone peptides. Using CRISPR-Cas9-mediated genome editing we find that BAZ1A and BAZ1B each recruit SMARCA5 to sites of damaged chromatin and promote survival. Genetic engineering of structure-designed bromodomain and plant homeodomain mutants reveals that reader modules of BAZ1A and BAZ1B, even when non-standard, are critical for DNA damage recovery in part by regulating ISWI factors loading at DNA lesions and supporting transcriptional programs required for survival.<br />ISWI chromatin remodelers regulate DNA accessibility and have been implicated in DNA damage repair. Here, the authors uncover functions, in response to DNA damage, for the bromodomain of the ISWI subunit BAZ1B and for the non-canonical PHD and bromodomain modules of the paralog BAZ1A.
- Subjects :
- 0301 basic medicine
BAZ1A
Chromosomal Proteins, Non-Histone
DNA damage
Science
General Physics and Astronomy
Biology
Article
General Biochemistry, Genetics and Molecular Biology
Cell Line
03 medical and health sciences
chemistry.chemical_compound
Humans
Nucleosome
Epigenetics
lcsh:Science
Transcription factor
Adenosine Triphosphatases
Gene Editing
Genetics
Multidisciplinary
Molecular Structure
DNA
General Chemistry
Chromatin
Bromodomain
Cell biology
030104 developmental biology
chemistry
lcsh:Q
CRISPR-Cas Systems
DNA Damage
Transcription Factors
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....2adcf10b22acb123783ab0fa64d7b957