DNA Damage Changes Distribution Pattern and Levels of HP1 Protein Isoforms in the Nucleolus and Increases Phosphorylation of HP1 beta-Ser88

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F19%3A00518331" target="_blank" >RIV/68081707:_____/19:00518331 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14740/19:00107962

Výsledek na webu

<a href="https://www.mdpi.com/2073-4409/8/9/1097/pdf" target="_blank" >https://www.mdpi.com/2073-4409/8/9/1097/pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cells8091097" target="_blank" >10.3390/cells8091097</a>

Jazyk výsledku

angličtina

Název v původním jazyce

DNA Damage Changes Distribution Pattern and Levels of HP1 Protein Isoforms in the Nucleolus and Increases Phosphorylation of HP1 beta-Ser88

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

DNA Damage Changes Distribution Pattern and Levels of HP1 Protein Isoforms in the Nucleolus and Increases Phosphorylation of HP1 beta-Ser88

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cells

ISSN

2073-4409

e-ISSN

—

Svazek periodika

8

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

22

Strana od-do

1097

Kód UT WoS článku

000489103800156

EID výsledku v databázi Scopus

—