Intracellular Formation of a DNA Damage-Induced, Histone Post-Translational Modification Following Bleomycin Treatment

Marco Paolo Jacinto; Stephen D. Fried; Marc M. Greenberg

doi:10.1021/jacs.2c02880

Intracellular Formation of a DNA Damage-Induced, Histone Post-Translational Modification Following Bleomycin Treatment

Marco Paolo Jacinto, Stephen D. Fried, Marc M. Greenberg

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

Abstract

Evaluating the significance of various forms of DNA damage is complicated by discoveries that some lesions inactivate repair enzymes or produce more deleterious forms of damage. Histone lysines within nucleosomes react with the commonly produced C4′-oxidized abasic site (C4-AP) to concomitantly yield an electrophilic modification (K_MP) on lysine and DNA strand scission. We developed a chemoproteomic approach to identify K_MPin HeLa cells. More than 60 000 K_MP-modified histones are produced per cell. Using LC-MS/MS, we detected K_MPat 17 of the 57 lysine residues distributed throughout the four core histone proteins. Therefore, K_MPconstitutes a DNA damage-induced, nonenzymatic histone post-translational modification. K_MPformation suggests that downstream processes resulting from DNA damage could have ramifications on cells.

Original language	English (US)
Pages (from-to)	7600-7605
Number of pages	6
Journal	Journal of the American Chemical Society
Volume	144
Issue number	17
DOIs	https://doi.org/10.1021/jacs.2c02880
State	Published - May 4 2022
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
Biochemistry
Catalysis
Colloid and Surface Chemistry

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10.1021/jacs.2c02880

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title = "Intracellular Formation of a DNA Damage-Induced, Histone Post-Translational Modification Following Bleomycin Treatment",

abstract = "Evaluating the significance of various forms of DNA damage is complicated by discoveries that some lesions inactivate repair enzymes or produce more deleterious forms of damage. Histone lysines within nucleosomes react with the commonly produced C4′-oxidized abasic site (C4-AP) to concomitantly yield an electrophilic modification (KMP) on lysine and DNA strand scission. We developed a chemoproteomic approach to identify KMPin HeLa cells. More than 60 000 KMP-modified histones are produced per cell. Using LC-MS/MS, we detected KMPat 17 of the 57 lysine residues distributed throughout the four core histone proteins. Therefore, KMPconstitutes a DNA damage-induced, nonenzymatic histone post-translational modification. KMPformation suggests that downstream processes resulting from DNA damage could have ramifications on cells.",

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AU - Greenberg, Marc M.

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AB - Evaluating the significance of various forms of DNA damage is complicated by discoveries that some lesions inactivate repair enzymes or produce more deleterious forms of damage. Histone lysines within nucleosomes react with the commonly produced C4′-oxidized abasic site (C4-AP) to concomitantly yield an electrophilic modification (KMP) on lysine and DNA strand scission. We developed a chemoproteomic approach to identify KMPin HeLa cells. More than 60 000 KMP-modified histones are produced per cell. Using LC-MS/MS, we detected KMPat 17 of the 57 lysine residues distributed throughout the four core histone proteins. Therefore, KMPconstitutes a DNA damage-induced, nonenzymatic histone post-translational modification. KMPformation suggests that downstream processes resulting from DNA damage could have ramifications on cells.

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Intracellular Formation of a DNA Damage-Induced, Histone Post-Translational Modification Following Bleomycin Treatment

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