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

J 2019

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

LEGARTOVÁ, Sofia, Gabriela LOCHMANOVÁ, Zbyněk ZDRÁHAL, Stanislav KOZUBEK, Jiří ŠPONER et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

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

Abstract

V originále

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 project

Name: Od konformace po biologické funkce proteinu HP1

Investor: Czech Science Foundation

LM2015043, research and development project

Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)

Investor: Ministry of Education, Youth and Sports of the CR

90043, large research infrastructures

Name: CIISB

Citovat

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.

@article{1600517,
   author = {Legartová, Sofia and Lochmanová, Gabriela and Zdráhal, Zbyněk and Kozubek, Stanislav and Šponer, Jiří and Krepl, Miroslav and Pokorná, Pavlína and Bártová, Eva},
   article_number = {9},
   doi = {http://dx.doi.org/10.3390/cells8091097},
   keywords = {HP1; irradiation; nucleolus; phosphorylation; mass spectrometry; epigenetics; FLIM-FRET},
   language = {eng},
   issn = {2073-4409},
   journal = {CELLS},
   title = {DNA Damage Changes Distribution Pattern and Levels of HP1 Protein Isoforms in the Nucleolus and Increases Phosphorylation of HP1 beta-Ser88},
   url = {https://www.mdpi.com/2073-4409/8/9/1097},
   volume = {8},
   year = {2019}
}

TY  - JOUR
ID  - 1600517
AU  - Legartová, Sofia - Lochmanová, Gabriela - Zdráhal, Zbyněk - Kozubek, Stanislav - Šponer, Jiří - Krepl, Miroslav - Pokorná, Pavlína - Bártová, Eva
PY  - 2019
TI  - DNA Damage Changes Distribution Pattern and Levels of HP1 Protein Isoforms in the Nucleolus and Increases Phosphorylation of HP1 beta-Ser88
JF  - CELLS
VL  - 8
IS  - 9
SP  - "1097"
EP  - "1097"
SN  - 20734409
KW  - HP1
KW  - irradiation
KW  - nucleolus
KW  - phosphorylation
KW  - mass spectrometry
KW  - epigenetics
KW  - FLIM-FRET
UR  - https://www.mdpi.com/2073-4409/8/9/1097
L2  - https://www.mdpi.com/2073-4409/8/9/1097
N2  - 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.
ER  -

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. \textit{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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