Sumoylation regulates EXO1 stability and processing of DNA
damage

J 2015

Sumoylation regulates EXO1 stability and processing of DNA damage

BOLOGNA, Serena, Veronika ALTMANNOVÁ, Emanuele VALTORTA, Christiane KOENIG, Prisca LIBERALI et. al.

Basic information

Original name

Sumoylation regulates EXO1 stability and processing of DNA damage

Authors

BOLOGNA, Serena (756 Switzerland), Veronika ALTMANNOVÁ (203 Czech Republic, belonging to the institution), Emanuele VALTORTA (380 Italy), Christiane KOENIG (756 Switzerland), Prisca LIBERALI (756 Switzerland), Christian GENTILI (756 Switzerland), Dorothea ANRATHER (40 Austria), Gustav AMMERER (40 Austria), Lucas PELKMANS (756 Switzerland), Lumír KREJČÍ (203 Czech Republic, guarantor, belonging to the institution) and Stefano FERRARI (756 Switzerland)

Edition

Cell Cycle, Philadelohia, TAYLOR & FRANCIS INC, 2015, 1538-4101

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

Genetics and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 3.952

RIV identification code

RIV/00216224:14110/15:00081061

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1080/15384101.2015.1060381

UT WoS

000359768900015

Keywords in English

chromosome aberrations; DNA resection; exonuclease-1; sumoylation; ubiquitylation

Abstract

V originále

DNA double-strand break repair by the error-free pathway of homologous recombination (HR) requires the concerted action of several factors. Among these, EXO1 and DNA2/BLM are responsible for the extensive resection of DNA ends to produce 3'-overhangs, which are essential intermediates for downstream steps of HR. Here we show that EXO1 is a SUMO target and that sumoylation affects EXO1 ubiquitylation and protein stability. We identify an UBC9-PIAS1/PIAS4-dependent mechanism controlling human EXO1 sumoylation in vivo and demonstrate conservation of this mechanism in yeast by the Ubc9-Siz1/Siz2 using an in vitro reconstituted system. Furthermore, we show physical interaction between EXO1 and the de-sumoylating enzyme SENP6 both in vitro and in vivo, promoting EXO1 stability. Finally, we identify the major sites of sumoylation in EXO1 and show that ectopic expression of a sumoylation-deficient form of EXO1 rescues the DNA damage-induced chromosomal aberrations observed upon wt-EXO1 expression. Thus, our study identifies a novel layer of regulation of EXO1, making the pathways that regulate its function an ideal target for therapeutic intervention.

Links

EE2.3.30.0009, research and development project

Name: Zaměstnáním čerstvých absolventů doktorského studia k vědecké excelenci

GAP207/12/2323, research and development project

Name: Endonuleazová a translokázová aktivita v restričních-modifikáčních komplexéch typu I

Investor: Czech Science Foundation

GA13-26629S, research and development project

Name: SUMO a stability genomu

Investor: Czech Science Foundation

Citovat

BOLOGNA, Serena, Veronika ALTMANNOVÁ, Emanuele VALTORTA, Christiane KOENIG, Prisca LIBERALI, Christian GENTILI, Dorothea ANRATHER, Gustav AMMERER, Lucas PELKMANS, Lumír KREJČÍ and Stefano FERRARI. Sumoylation regulates EXO1 stability and processing of DNA damage. Cell Cycle. Philadelohia: TAYLOR & FRANCIS INC, 2015, vol. 14, No 15, p. 2439-2450. ISSN 1538-4101. Available from: https://dx.doi.org/10.1080/15384101.2015.1060381.

@article{1312489,
   author = {Bologna, Serena and Altmannová, Veronika and Valtorta, Emanuele and Koenig, Christiane and Liberali, Prisca and Gentili, Christian and Anrather, Dorothea and Ammerer, Gustav and Pelkmans, Lucas and Krejčí, Lumír and Ferrari, Stefano},
   article_location = {Philadelohia},
   article_number = {15},
   doi = {http://dx.doi.org/10.1080/15384101.2015.1060381},
   keywords = {chromosome aberrations; DNA resection; exonuclease-1; sumoylation; ubiquitylation},
   language = {eng},
   issn = {1538-4101},
   journal = {Cell Cycle},
   title = {Sumoylation regulates EXO1 stability and processing of DNA damage},
   volume = {14},
   year = {2015}
}

TY  - JOUR
ID  - 1312489
AU  - Bologna, Serena - Altmannová, Veronika - Valtorta, Emanuele - Koenig, Christiane - Liberali, Prisca - Gentili, Christian - Anrather, Dorothea - Ammerer, Gustav - Pelkmans, Lucas - Krejčí, Lumír - Ferrari, Stefano
PY  - 2015
TI  - Sumoylation regulates EXO1 stability and processing of DNA damage
JF  - Cell Cycle
VL  - 14
IS  - 15
SP  - 2439-2450
EP  - 2439-2450
PB  - TAYLOR & FRANCIS INC
SN  - 15384101
KW  - chromosome aberrations
KW  - DNA resection
KW  - exonuclease-1
KW  - sumoylation
KW  - ubiquitylation
N2  - DNA double-strand break repair by the error-free pathway of homologous recombination (HR) requires the concerted action of several factors. Among these, EXO1 and DNA2/BLM are responsible for the extensive resection of DNA ends to produce 3'-overhangs, which are essential intermediates for downstream steps of HR. Here we show that EXO1 is a SUMO target and that sumoylation affects EXO1 ubiquitylation and protein stability. We identify an UBC9-PIAS1/PIAS4-dependent mechanism controlling human EXO1 sumoylation in vivo and demonstrate conservation of this mechanism in yeast by the Ubc9-Siz1/Siz2 using an in vitro reconstituted system. Furthermore, we show physical interaction between EXO1 and the de-sumoylating enzyme SENP6 both in vitro and in vivo, promoting EXO1 stability. Finally, we identify the major sites of sumoylation in EXO1 and show that ectopic expression of a sumoylation-deficient form of EXO1 rescues the DNA damage-induced chromosomal aberrations observed upon wt-EXO1 expression. Thus, our study identifies a novel layer of regulation of EXO1, making the pathways that regulate its function an ideal target for therapeutic intervention.
ER  -

BOLOGNA, Serena, Veronika ALTMANNOVÁ, Emanuele VALTORTA, Christiane KOENIG, Prisca LIBERALI, Christian GENTILI, Dorothea ANRATHER, Gustav AMMERER, Lucas PELKMANS, Lumír KREJČÍ and Stefano FERRARI. Sumoylation regulates EXO1 stability and processing of DNA damage. \textit{Cell Cycle}. Philadelohia: TAYLOR \&{} FRANCIS INC, 2015, vol.~14, No~15, p.~2439-2450. ISSN~1538-4101. Available from: https://dx.doi.org/10.1080/15384101.2015.1060381.

Detailed Information on Publication Record