Heat-induced SIRT1-mediated H4K16ac deacetylation impairs resection and SMARCAD1 recruitment to double strand breaks

S Chakraborti; Mayank Singh; Raj K. Pandita; Vipin Singh; Calvin Lo; francesca leonard; Nobuo Horikoshi; E Moros; Deblina Guha; C Hunt; Eric Chau; Kazi M. Ahmed; Prayas Sethi; Vijaya Charaka; Biana Godin; Kalpana Makhijani; Harry Schertan; Jeanette Deck; Michael Hausmann; Arjamand Mushtaq; Mohammad Altaf; Kenneth S. Ramos; Krishna M. Bhat; Nitika Taneja; Chandrima Das; TK Pandita

Heat-induced SIRT1-mediated H4K16ac deacetylation impairs resection and SMARCAD1 recruitment to double strand breaks

S Chakraborti
, Mayank Singh
, Raj K. Pandita
, Vipin Singh
, Calvin Lo
, francesca leonard
, Nobuo Horikoshi
, E Moros
, Deblina Guha
, C Hunt
, Eric Chau
, Kazi M. Ahmed
, Prayas Sethi
, Vijaya Charaka
, Biana Godin
, Kalpana Makhijani
, Harry Schertan
, Jeanette Deck
, Michael Hausmann
, Arjamand Mushtaq

Mohammad Altaf, Kenneth S. Ramos, Krishna M. Bhat, Nitika Taneja, Chandrima Das, TK Pandita^*

^*Corresponding author for this work

Molecular Genetics

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Hyperthermia inhibits DNA double-strand break (DSB) repair that utilizes homol
ogous recombination (HR) pathway by a poorly defined mechanism(s); however,
themechanismsforthisinhibition remain unclear.Here wereportthat hyperther
miadecreasesH4K16acetylation(H4K16ac),anepigeneticmodificationessential
for genome stability and transcription. Heat-induced reduction in H4K16ac was
detected in humans, Drosophila, and yeast, indicating that this is a highly
conservedresponse.Theexaminationofhistonedeacetylaserecruitmenttochro
matin after heat-shock identified SIRT1 as the major deacetylase subsequently
enriched at gene-rich regions. Heat-induced SIRT1 recruitment was antagonized
bychromatinremodelerSMARCAD1depletionand,likehyperthermia,thedeple
tion of the SMARCAD1 or combination of the two impaired DNA end resection
and increased replication stress. Altered repair protein recruitment was associ
ated with heat-shock-induced g-H2AX chromatin changes and DSB repair pro
cessing. Theseresultssupportanovelmechanismwherebyhyperthermiaimpacts
chromatin organization owing to H4K16ac deacetylation, negatively affecting
the HR-dependent DSB repair.

Original language	English
Article number	104142
Pages (from-to)	1-24
Number of pages	24
Journal	iScience
Volume	25
Issue number	4
Early online date	23 Mar 2022
Publication status	Published - 15 Apr 2022

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1-s2.0-S2589004222004126-mainFinal published version, 5.71 MBLicence: CC BY

https://www.sciencedirect.com/science/article/pii/S2589004222004126Licence: CC BY

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Chakraborti, S., Singh, M., Pandita, R. K., Singh, V., Lo, C., leonard, F., Horikoshi, N., Moros, E., Guha, D., Hunt, C., Chau, E., Ahmed, K. M., Sethi, P., Charaka, V., Godin, B., Makhijani, K., Schertan, H., Deck, J., Hausmann, M., ... Pandita, TK. (2022). Heat-induced SIRT1-mediated H4K16ac deacetylation impairs resection and SMARCAD1 recruitment to double strand breaks. iScience, 25(4), 1-24. Article 104142. https://www.sciencedirect.com/science/article/pii/S2589004222004126

@article{f052799c19014e1a8270c70d13643244,

title = "Heat-induced SIRT1-mediated H4K16ac deacetylation impairs resection and SMARCAD1 recruitment to double strand breaks",

abstract = " Hyperthermia inhibits DNA double-strand break (DSB) repair that utilizes homol ogous recombination (HR) pathway by a poorly defined mechanism(s); however, themechanismsforthisinhibition remain unclear.Here wereportthat hyperther miadecreasesH4K16acetylation(H4K16ac),anepigeneticmodificationessential for genome stability and transcription. Heat-induced reduction in H4K16ac was detected in humans, Drosophila, and yeast, indicating that this is a highly conservedresponse.Theexaminationofhistonedeacetylaserecruitmenttochro matin after heat-shock identified SIRT1 as the major deacetylase subsequently enriched at gene-rich regions. Heat-induced SIRT1 recruitment was antagonized bychromatinremodelerSMARCAD1depletionand,likehyperthermia,thedeple tion of the SMARCAD1 or combination of the two impaired DNA end resection and increased replication stress. Altered repair protein recruitment was associ ated with heat-shock-induced g-H2AX chromatin changes and DSB repair pro cessing. Theseresultssupportanovelmechanismwherebyhyperthermiaimpacts chromatin organization owing to H4K16ac deacetylation, negatively affecting the HR-dependent DSB repair.",

author = "S Chakraborti and Mayank Singh and Pandita, \{Raj K.\} and Vipin Singh and Calvin Lo and francesca leonard and Nobuo Horikoshi and E Moros and Deblina Guha and C Hunt and Eric Chau and Ahmed, \{Kazi M.\} and Prayas Sethi and Vijaya Charaka and Biana Godin and Kalpana Makhijani and Harry Schertan and Jeanette Deck and Michael Hausmann and Arjamand Mushtaq and Mohammad Altaf and Ramos, \{Kenneth S.\} and Bhat, \{Krishna M.\} and Nitika Taneja and Chandrima Das and TK Pandita",

year = "2022",

month = apr,

day = "15",

language = "English",

volume = "25",

pages = "1--24",

journal = "iScience",

issn = "2589-0042",

publisher = "Elsevier Inc.",

number = "4",

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Chakraborti, S, Singh, M, Pandita, RK, Singh, V, Lo, C, leonard, F, Horikoshi, N, Moros, E, Guha, D, Hunt, C, Chau, E, Ahmed, KM, Sethi, P, Charaka, V, Godin, B, Makhijani, K, Schertan, H, Deck, J, Hausmann, M, Mushtaq, A, Altaf, M, Ramos, KS, Bhat, KM, Taneja, N, Das, C & Pandita, TK 2022, 'Heat-induced SIRT1-mediated H4K16ac deacetylation impairs resection and SMARCAD1 recruitment to double strand breaks', iScience, vol. 25, no. 4, 104142, pp. 1-24. <https://www.sciencedirect.com/science/article/pii/S2589004222004126>

TY - JOUR

T1 - Heat-induced SIRT1-mediated H4K16ac deacetylation impairs resection and SMARCAD1 recruitment to double strand breaks

AU - Chakraborti, S

AU - Singh, Mayank

AU - Pandita, Raj K.

AU - Singh, Vipin

AU - Lo, Calvin

AU - leonard, francesca

AU - Horikoshi, Nobuo

AU - Moros, E

AU - Guha, Deblina

AU - Hunt, C

AU - Chau, Eric

AU - Ahmed, Kazi M.

AU - Sethi, Prayas

AU - Charaka, Vijaya

AU - Godin, Biana

AU - Makhijani, Kalpana

AU - Schertan, Harry

AU - Deck, Jeanette

AU - Hausmann, Michael

AU - Mushtaq, Arjamand

AU - Altaf, Mohammad

AU - Ramos, Kenneth S.

AU - Bhat, Krishna M.

AU - Taneja, Nitika

AU - Das, Chandrima

AU - Pandita, TK

PY - 2022/4/15

Y1 - 2022/4/15

N2 - Hyperthermia inhibits DNA double-strand break (DSB) repair that utilizes homol ogous recombination (HR) pathway by a poorly defined mechanism(s); however, themechanismsforthisinhibition remain unclear.Here wereportthat hyperther miadecreasesH4K16acetylation(H4K16ac),anepigeneticmodificationessential for genome stability and transcription. Heat-induced reduction in H4K16ac was detected in humans, Drosophila, and yeast, indicating that this is a highly conservedresponse.Theexaminationofhistonedeacetylaserecruitmenttochro matin after heat-shock identified SIRT1 as the major deacetylase subsequently enriched at gene-rich regions. Heat-induced SIRT1 recruitment was antagonized bychromatinremodelerSMARCAD1depletionand,likehyperthermia,thedeple tion of the SMARCAD1 or combination of the two impaired DNA end resection and increased replication stress. Altered repair protein recruitment was associ ated with heat-shock-induced g-H2AX chromatin changes and DSB repair pro cessing. Theseresultssupportanovelmechanismwherebyhyperthermiaimpacts chromatin organization owing to H4K16ac deacetylation, negatively affecting the HR-dependent DSB repair.

AB - Hyperthermia inhibits DNA double-strand break (DSB) repair that utilizes homol ogous recombination (HR) pathway by a poorly defined mechanism(s); however, themechanismsforthisinhibition remain unclear.Here wereportthat hyperther miadecreasesH4K16acetylation(H4K16ac),anepigeneticmodificationessential for genome stability and transcription. Heat-induced reduction in H4K16ac was detected in humans, Drosophila, and yeast, indicating that this is a highly conservedresponse.Theexaminationofhistonedeacetylaserecruitmenttochro matin after heat-shock identified SIRT1 as the major deacetylase subsequently enriched at gene-rich regions. Heat-induced SIRT1 recruitment was antagonized bychromatinremodelerSMARCAD1depletionand,likehyperthermia,thedeple tion of the SMARCAD1 or combination of the two impaired DNA end resection and increased replication stress. Altered repair protein recruitment was associ ated with heat-shock-induced g-H2AX chromatin changes and DSB repair pro cessing. Theseresultssupportanovelmechanismwherebyhyperthermiaimpacts chromatin organization owing to H4K16ac deacetylation, negatively affecting the HR-dependent DSB repair.

M3 - Article

SN - 2589-0042

VL - 25

SP - 1

EP - 24

JO - iScience

JF - iScience

IS - 4

M1 - 104142

ER -

Heat-induced SIRT1-mediated H4K16ac deacetylation impairs resection and SMARCAD1 recruitment to double strand breaks

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