Journal
ISCIENCE
Volume 25, Issue 4, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2022.104142
Keywords
-
Categories
Funding
- NIH [RO1 CA154320, RO1 CA129537, RO1 GM109768, PO1 CA104457]
- SwarnaJayanti Fellowship, Department of Science and Technology [DST/SJF/LSA-02/2017-18]
- Department of Biotechnology [BT/PR28920/MED/122/176/2018, BT/HRD-NBA-NWB/38/2019-20]
- Department of Atomic Energy, Government of India (DAE), Govt. of India [RSI 4002]
- NWO-Incentive Grant [12412]
- FKZ of the German Federal Ministry of Education and Research [02NUK058A]
Ask authors/readers for more resources
This study finds that hyperthermia can inhibit DNA double-strand break repair that utilizes homologous recombination by reducing H4K16 acetylation and impacting chromatin organization. This discovery is important for understanding the effects of hyperthermia on genome stability.
Hyperthermia inhibits DNA double-strand break (DSB) repair that utilizes homologous recombination (HR) pathway by a poorly defined mechanism(s); however, themechanisms for this inhibition remain unclear. Here we report that hyperthermia decreases H4K16 acetylation (H4K16ac), an epigenetic modification essential for genome stability and transcription. Heat-induced reduction in H4K16ac was detected in humans, Drosophila, and yeast, indicating that this is a highly conserved response. The examination of histone deacetylase recruitment to chromatin after heat-shock identified SIRT1 as the major deacetylase subsequently enriched at gene-rich regions. Heat-induced SIRT1 recruitment was antagonized by chromatin remodeler SMARCAD1 depletion and, like hyperthermia, the depletion of the SMARCAD1 or combination of the two impaired DNA end resection and increased replication stress. Altered repair protein recruitment was associated with heat-shock-induced gamma-H2AX chromatin changes and DSB repair processing. These results support a novel mechanismwhereby hyperthermia impacts chromatin organization owing to H4K16ac deacetylation, negatively affecting the HR-dependent DSB repair.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available