iScience (Apr 2022)
Heat-induced SIRT1-mediated H4K16ac deacetylation impairs resection and SMARCAD1 recruitment to double strand breaks
- Sharmistha Chakraborty,
- Mayank Singh,
- Raj K. Pandita,
- Vipin Singh,
- Calvin S.C. Lo,
- Fransisca Leonard,
- Nobuo Horikoshi,
- Eduardo G. Moros,
- Deblina Guha,
- Clayton R. Hunt,
- Eric Chau,
- Kazi M. Ahmed,
- Prayas Sethi,
- Vijaya Charaka,
- Biana Godin,
- Kalpana Makhijani,
- Harry Scherthan,
- Jeanette Deck,
- Michael Hausmann,
- Arjamand Mushtaq,
- Mohammad Altaf,
- Kenneth S. Ramos,
- Krishna M. Bhat,
- Nitika Taneja,
- Chandrima Das,
- Tej K. Pandita
Affiliations
- Sharmistha Chakraborty
- Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Radiation Oncology, University of Texas Southwestern Medical Centre, Dallas, TX, USA
- Mayank Singh
- Department of Radiation Oncology, University of Texas Southwestern Medical Centre, Dallas, TX, USA; Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi 110029, India
- Raj K. Pandita
- Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Radiation Oncology, University of Texas Southwestern Medical Centre, Dallas, TX, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Departments of Radiation Oncology, Washington University, St Louis, MO, USA
- Vipin Singh
- Biophysics & Structural Genomics Division Saha Institute of Nuclear Physics, Bidhan Nagar, Kolkata, West Bengal 700064, India; Homi Bhaba National Institute, Mumbai, India
- Calvin S.C. Lo
- Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 Rotterdam, CA, the Netherlands
- Fransisca Leonard
- Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA
- Nobuo Horikoshi
- Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Radiation Oncology, University of Texas Southwestern Medical Centre, Dallas, TX, USA; Departments of Radiation Oncology, Washington University, St Louis, MO, USA
- Eduardo G. Moros
- Departments of Radiation Oncology, Washington University, St Louis, MO, USA; Departments of Radiation Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA
- Deblina Guha
- Biophysics & Structural Genomics Division Saha Institute of Nuclear Physics, Bidhan Nagar, Kolkata, West Bengal 700064, India
- Clayton R. Hunt
- Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Radiation Oncology, University of Texas Southwestern Medical Centre, Dallas, TX, USA; Departments of Radiation Oncology, Washington University, St Louis, MO, USA
- Eric Chau
- Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA
- Kazi M. Ahmed
- Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA
- Prayas Sethi
- Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi 110029, India
- Vijaya Charaka
- Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA
- Biana Godin
- Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA
- Kalpana Makhijani
- Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA
- Harry Scherthan
- Bundeswehr Institute of Radiobiology Affiliated to the University of Ulm, Neuherbergstr. 11, 80937 Munich, Germany
- Jeanette Deck
- Kirchhoff-Institute for Physics, Heidelberg University, Im Neuenheimer Feld 227, 69120 Heidelberg, Germany
- Michael Hausmann
- Kirchhoff-Institute for Physics, Heidelberg University, Im Neuenheimer Feld 227, 69120 Heidelberg, Germany
- Arjamand Mushtaq
- Department of Biotechnology, University of Kashmir, Srinagar, Jammu and Kashmir 190006, India
- Mohammad Altaf
- Department of Biotechnology, University of Kashmir, Srinagar, Jammu and Kashmir 190006, India
- Kenneth S. Ramos
- Center for Genomics and Precision Medicine, Texas A&M College of Medicine, Houston, TX, USA
- Krishna M. Bhat
- Department of Molecular Medicine, University of South Florida, Tampa, FL 33612, USA
- Nitika Taneja
- Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3000 Rotterdam, CA, the Netherlands
- Chandrima Das
- Biophysics & Structural Genomics Division Saha Institute of Nuclear Physics, Bidhan Nagar, Kolkata, West Bengal 700064, India; Homi Bhaba National Institute, Mumbai, India; Corresponding author
- Tej K. Pandita
- Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Radiation Oncology, University of Texas Southwestern Medical Centre, Dallas, TX, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Departments of Radiation Oncology, Washington University, St Louis, MO, USA; Center for Genomics and Precision Medicine, Texas A&M College of Medicine, Houston, TX, USA; Corresponding author
- Journal volume & issue
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Vol. 25,
no. 4
p. 104142
Abstract
Summary: Hyperthermia inhibits DNA double-strand break (DSB) repair that utilizes homologous recombination (HR) pathway by a poorly defined mechanism(s); however, the mechanisms 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 γ-H2AX chromatin changes and DSB repair processing. These results support a novel mechanism whereby hyperthermia impacts chromatin organization owing to H4K16ac deacetylation, negatively affecting the HR-dependent DSB repair.
