LEGARTOVÁ, Sofia, Gabriela LOCHMANOVÁ, Zbyněk ZDRÁHAL, Stanislav KOZUBEK, Jiří ŠPONER, Miroslav KREPL, Pavlína POKORNÁ and Eva BÁRTOVÁ. DNA Damage Changes Distribution Pattern and Levels of HP1 Protein Isoforms in the Nucleolus and Increases Phosphorylation of HP1 beta-Ser88. CELLS. 2019, vol. 8, No 9, p. "1097", 22 pp. ISSN 2073-4409. Available from: https://dx.doi.org/10.3390/cells8091097.
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Basic information
Original name DNA Damage Changes Distribution Pattern and Levels of HP1 Protein Isoforms in the Nucleolus and Increases Phosphorylation of HP1 beta-Ser88
Authors LEGARTOVÁ, Sofia, Gabriela LOCHMANOVÁ (203 Czech Republic, belonging to the institution), Zbyněk ZDRÁHAL (203 Czech Republic, guarantor, belonging to the institution), Stanislav KOZUBEK (203 Czech Republic), Jiří ŠPONER (203 Czech Republic), Miroslav KREPL (203 Czech Republic), Pavlína POKORNÁ (203 Czech Republic) and Eva BÁRTOVÁ (203 Czech Republic).
Edition CELLS, 2019, 2073-4409.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10601 Cell biology
Country of publisher Switzerland
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 4.366
RIV identification code RIV/00216224:14740/19:00107962
Organization unit Central European Institute of Technology
Doi http://dx.doi.org/10.3390/cells8091097
UT WoS 000489103800156
Keywords in English HP1; irradiation; nucleolus; phosphorylation; mass spectrometry; epigenetics; FLIM-FRET
Tags CF PROT, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Pavla Foltynová, Ph.D., učo 106624. Changed: 19/2/2020 16:43.
Abstract
The family of heterochromatin protein 1 (HP1) isoforms is essential for chromatin packaging, regulation of gene expression, and repair of damaged DNA. Here we document that gamma-radiation reduced the number of HP1 alpha-positive foci, but not HP1 beta and HP1 gamma foci, located in the vicinity of the fibrillarin-positive region of the nucleolus. The additional analysis confirmed that gamma-radiation has the ability to significantly decrease the level of HP1 alpha in rDNA promoter and rDNA encoding 28S rRNA. By mass spectrometry, we showed that treatment by gamma-rays enhanced the HP1 beta serine 88 phosphorylation (S88ph), but other analyzed modifications of HP1 beta, including S161ph/Y163ph, S171ph, and S174ph, were not changed in cells exposed to gamma-rays or treated by the HDAC inhibitor (HDACi). Interestingly, a combination of HDACi and gamma-radiation increased the level of HP1 alpha and HP1 gamma. The level of HP1 beta remained identical before and after the HDACi/gamma-rays treatment, but HDACi strengthened HP1 beta interaction with the KRAB-associated protein 1 (KAP1) protein. Conversely, HP1 gamma did not interact with KAP1, although approximately 40% of HP1 gamma foci co-localized with accumulated KAP1. Especially HP1 gamma foci at the periphery of nucleoli were mostly absent of KAP1. Together, DNA damage changed the morphology, levels, and interaction properties of HP1 isoforms. Also, gamma-irradiation-induced hyperphosphorylation of the HP1 beta protein; thus, HP1 beta-S88ph could be considered as an important marker of DNA damage.
Links
GA18-07384S, research and development projectName: Od konformace po biologické funkce proteinu HP1
Investor: Czech Science Foundation
LM2015043, research and development projectName: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)
Investor: Ministry of Education, Youth and Sports of the CR
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