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.

Základní údaje

Originální název

Sumoylation regulates EXO1 stability and processing of DNA damage

Autoři

BOLOGNA, Serena (756 Švýcarsko), Veronika ALTMANNOVÁ (203 Česká republika, domácí), Emanuele VALTORTA (380 Itálie), Christiane KOENIG (756 Švýcarsko), Prisca LIBERALI (756 Švýcarsko), Christian GENTILI (756 Švýcarsko), Dorothea ANRATHER (40 Rakousko), Gustav AMMERER (40 Rakousko), Lucas PELKMANS (756 Švýcarsko), Lumír KREJČÍ (203 Česká republika, garant, domácí) a Stefano FERRARI (756 Švýcarsko)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

Genetika a molekulární biologie

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 3.952

Kód RIV

RIV/00216224:14110/15:00081061

Organizační jednotka

Lékařská fakulta

DOI

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

UT WoS

000359768900015

Klíčová slova anglicky

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

Štítky

EL OK, podil

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 29. 9. 2015 13:06, Ing. Mgr. Věra Pospíšilíková

Anotace

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.

Návaznosti

EE2.3.30.0009, projekt VaV

Název: Zaměstnáním čerstvých absolventů doktorského studia k vědecké excelenci

GAP207/12/2323, projekt VaV

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

Investor: Grantová agentura ČR, Endonuleázová a translokázová aktivita v restrikčních-modifikačních komplexech typu I

GA13-26629S, projekt VaV

Název: SUMO a stability genomu

Investor: Grantová agentura ČR, SUMO a stability genomu

Citovat

BOLOGNA, Serena, Veronika ALTMANNOVÁ, Emanuele VALTORTA, Christiane KOENIG, Prisca LIBERALI, Christian GENTILI, Dorothea ANRATHER, Gustav AMMERER, Lucas PELKMANS, Lumír KREJČÍ a Stefano FERRARI. Sumoylation regulates EXO1 stability and processing of DNA damage. Cell Cycle. Philadelohia: TAYLOR & FRANCIS INC, 2015, roč. 14, č. 15, s. 2439-2450. ISSN 1538-4101. Dostupné z: 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 a Stefano FERRARI. Sumoylation regulates EXO1 stability and processing of DNA damage. \textit{Cell Cycle}. Philadelohia: TAYLOR \&{} FRANCIS INC, 2015, roč.~14, č.~15, s.~2439-2450. ISSN~1538-4101. Dostupné z: https://dx.doi.org/10.1080/15384101.2015.1060381.

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