The HSF1–PARP13–PARP1 complex facilitates DNA repair and promotes mammary tumorigenesis
| Autor: | Katsuhiko Shirahige, Ryuichiro Nakato, Ryosuke Takii, Akira Nakai, Arpit Katiyar, Eiichi Takaki, Mitsuaki Fujimoto |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genome instability DNA Repair Carcinogenesis DNA repair DNA damage Science Poly ADP ribose polymerase Poly (ADP-Ribose) Polymerase-1 General Physics and Astronomy Breast Neoplasms Article Genomic Instability General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences chemistry.chemical_compound PARP1 Heat Shock Transcription Factors Animals Humans lcsh:Science Polymerase Multidisciplinary biology BRCA1 Protein Chemistry RNA-Binding Proteins General Chemistry Chromatin Cell biology 030104 developmental biology biology.protein lcsh:Q Female DNA DNA Damage Protein Binding |
| Zdroj: | Nature Communications, Vol 8, Iss 1, Pp 1-16 (2017) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-017-01807-7 |
| Popis: | Poly(ADP-ribose) polymerase 1 (PARP1) is involved in DNA repair, chromatin structure, and transcription. However, the mechanisms that regulate PARP1 distribution on DNA are poorly understood. Here, we show that heat shock transcription factor 1 (HSF1) recruits PARP1 through the scaffold protein PARP13. In response to DNA damage, activated and auto-poly-ADP-ribosylated PARP1 dissociates from HSF1–PARP13, and redistributes to DNA lesions and DNA damage-inducible gene loci. Histone deacetylase 1 maintains PARP1 in the ternary complex by inactivating PARP1 through deacetylation. Blocking ternary complex formation impairs redistribution of PARP1 during DNA damage, which reduces gene expression and DNA repair. Furthermore, ternary complex formation and PARP1 redistribution protect cells from DNA damage by promoting DNA repair, and support growth of BRCA1-null mammary tumors, which are sensitive to PARP inhibitors. Our findings identify HSF1 as a regulator of genome integrity and define this function as a guarding mechanism for a specific type of mammary tumorigenesis. PARP1 recruitment to DNA lesions is critical for DNA damage repair but how DNA damage induces PARP1 redistribution is largely unknown. Here, the authors provide evidence that PARP1 redistribution and DNA repair in tumor cells depend on the formation of a HSF1–PARP13–PARP1 complex. |
| Databáze: | OpenAIRE |
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