Universität zu Köln

Mandemaker, Imke K., Geijer, Marit E., Kik, Iris, Bezstarosti, Karel, Rijkers, Erikjan, Raams, Anja, Janssens, Roel C., Lans, Hannes ORCID: 0000-0003-4417-5358, Hoeijmakers, Jan H. J., Demmers, Jeroen A. A., Vermeulen, Wim ORCID: 0000-0003-3616-734X and Marteijn, Jurgen A. (2018). DNA damage-induced replication stress results in PA200-proteasome-mediated degradation of acetylated histones. EMBO Rep., 19 (10). HOBOKEN: WILEY. ISSN 1469-3178

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Abstract

Histone acetylation influences protein interactions and chromatin accessibility and plays an important role in the regulation of transcription, replication, and DNA repair. Conversely, DNA damage affects these crucial cellular processes and induces changes in histone acetylation. However, a comprehensive overview of the effects of DNA damage on the histone acetylation landscape is currently lacking. To quantify changes in histone acetylation, we developed an unbiased quantitative mass spectrometry analysis on affinity-purified acetylated histone peptides, generated by differential parallel proteolysis. We identify a large number of histone acetylation sites and observe an overall reduction of acetylated histone residues in response to DNA damage, indicative of a histone-wide loss of acetyl modifications. This decrease is mainly caused by DNA damage-induced replication stress coupled to specific proteasome-dependent loss of acetylated histones. Strikingly, this degradation of acetylated histones is independent of ubiquitylation but requires the PA200-proteasome activator, a complex that specifically targets acetylated histones for degradation. The uncovered replication stress-induced degradation of acetylated histones represents an important chromatin-modifying response to cope with replication stress.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mandemaker, Imke K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Geijer, Marit E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kik, Iris UNSPECIFIED UNSPECIFIED UNSPECIFIED Bezstarosti, Karel UNSPECIFIED UNSPECIFIED UNSPECIFIED Rijkers, Erikjan UNSPECIFIED UNSPECIFIED UNSPECIFIED Raams, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED Janssens, Roel C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lans, Hannes UNSPECIFIED orcid.org/0000-0003-4417-5358 UNSPECIFIED Hoeijmakers, Jan H. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Demmers, Jeroen A. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vermeulen, Wim UNSPECIFIED orcid.org/0000-0003-3616-734X UNSPECIFIED Marteijn, Jurgen A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-170189
DOI:	10.15252/embr.201745566
Journal or Publication Title:	EMBO Rep.
Volume:	19
Number:	10
Date:	2018
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1469-3178
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NUCLEOTIDE EXCISION-REPAIR; UV-IRRADIATION; HOMOLOGOUS RECOMBINATION; PROTEIN INTERACTIONS; CHROMATIN-STRUCTURE; BINDING-PROTEIN; P48 SUBUNIT; HUMAN-CELLS; NUCLEOSOME; TRANSCRIPTION Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/17018