Sumoylation regulates the stability and nuclease activity of
Saccharomyces cerevisiae Dna2

J 2019

Sumoylation regulates the stability and nuclease activity of Saccharomyces cerevisiae Dna2

RANJHA, Lepakshi, Maryna LEVIKOVA, Veronika ALTMANNOVÁ, Lumír KREJČÍ, Petr CEJKA et. al.

Základní údaje

Originální název

Sumoylation regulates the stability and nuclease activity of Saccharomyces cerevisiae Dna2

Autoři

RANJHA, Lepakshi (756 Švýcarsko), Maryna LEVIKOVA (756 Švýcarsko), Veronika ALTMANNOVÁ (203 Česká republika, domácí), Lumír KREJČÍ (203 Česká republika, domácí) a Petr CEJKA (garant)

Vydání

COMMUNICATIONS BIOLOGY, NEW YORK, NATURE PUBLISHING GROUP, 2019, 2399-3642

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.165

Kód RIV

RIV/00216224:14110/19:00108020

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1038/s42003-019-0428-0

UT WoS

000467215700004

Klíčová slova anglicky

SINGLE-STRANDED-DNA; END-RESECTION; IN-VIVO; SECONDARY STRUCTURE; OKAZAKI FRAGMENTS; REPLICATION FORKS; EXONUCLEASE 1; SUMO; HELICASE; PROTEIN

Štítky

14110513

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 4. 3. 2020 14:24, Mgr. Tereza Miškechová

Anotace

V originále

Dna2 is an essential nuclease-helicase that acts in several distinct DNA metabolic pathways including DNA replication and recombination. To balance these functions and prevent unscheduled DNA degradation, Dna2 activities must be regulated. Here we show that Saccharomyces cerevisiae Dna2 function is controlled by sumoylation. We map the sumoylation sites to the N-terminal regulatory domain of Dna2 and show that in vitro sumoylation of recombinant Dna2 impairs its nuclease but not helicase activity. In cells, the total levels of the non-sumoylatable Dna2 variant are elevated. However, non-sumoylatable Dna2 shows impaired nuclear localization and reduced recruitment to foci upon DNA damage. Non-sumoylatable Dna2 reduces the rate of DNA end resection, as well as impedes cell growth and cell cycle progression through S phase. Taken together, these findings show that in addition to Dna2 phosphorylation described previously, Dna2 sumoylation is required for the homeostasis of the Dna2 protein function to promote genome stability.

Návaznosti

EF16_025/0007381, projekt VaV

Název: Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou

GA17-17720S, projekt VaV

Název: Vnitřní vlastnosti RAD51 vlákna a jeho biologické regulace

Investor: Grantová agentura ČR, Vnitřní vlastnosti RAD51 vlákna a jeho biologické regulace

MUNI/A/1087/2018, interní kód MU

Název: Molekulární a buněčná biologie pro biomedicínské vědy

Investor: Masarykova univerzita, Molekulární a buněčná biologie pro biomedicínské vědy, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

206292/E/17/Z, interní kód MU

Název: Mechanics and execution of homologous recombination - biophysics to the organism

Investor: Wellcome Trust, Mechanics and execution of homologous recombination - biophysics to the organism

Citovat

RANJHA, Lepakshi, Maryna LEVIKOVA, Veronika ALTMANNOVÁ, Lumír KREJČÍ a Petr CEJKA. Sumoylation regulates the stability and nuclease activity of Saccharomyces cerevisiae Dna2. COMMUNICATIONS BIOLOGY. NEW YORK: NATURE PUBLISHING GROUP, 2019, roč. 2, MAY 8 2019, s. 1-12. ISSN 2399-3642. Dostupné z: https://dx.doi.org/10.1038/s42003-019-0428-0.

@article{1603896,
   author = {Ranjha, Lepakshi and Levikova, Maryna and Altmannová, Veronika and Krejčí, Lumír and Cejka, Petr},
   article_location = {NEW YORK},
   article_number = {MAY 8 2019},
   doi = {http://dx.doi.org/10.1038/s42003-019-0428-0},
   keywords = {SINGLE-STRANDED-DNA; END-RESECTION; IN-VIVO; SECONDARY STRUCTURE; OKAZAKI FRAGMENTS; REPLICATION FORKS; EXONUCLEASE 1; SUMO; HELICASE; PROTEIN},
   language = {eng},
   issn = {2399-3642},
   journal = {COMMUNICATIONS BIOLOGY},
   title = {Sumoylation regulates the stability and nuclease activity of Saccharomyces cerevisiae Dna2},
   url = {http://dx.doi.org/10.1038/s42003-019-0428-0},
   volume = {2},
   year = {2019}
}

TY  - JOUR
ID  - 1603896
AU  - Ranjha, Lepakshi - Levikova, Maryna - Altmannová, Veronika - Krejčí, Lumír - Cejka, Petr
PY  - 2019
TI  - Sumoylation regulates the stability and nuclease activity of Saccharomyces cerevisiae Dna2
JF  - COMMUNICATIONS BIOLOGY
VL  - 2
IS  - MAY 8 2019
SP  - 1-12
EP  - 1-12
PB  - NATURE PUBLISHING GROUP
SN  - 23993642
KW  - SINGLE-STRANDED-DNA
KW  - END-RESECTION
KW  - IN-VIVO
KW  - SECONDARY STRUCTURE
KW  - OKAZAKI FRAGMENTS
KW  - REPLICATION FORKS
KW  - EXONUCLEASE 1
KW  - SUMO
KW  - HELICASE
KW  - PROTEIN
UR  - http://dx.doi.org/10.1038/s42003-019-0428-0
L2  - http://dx.doi.org/10.1038/s42003-019-0428-0
N2  - Dna2 is an essential nuclease-helicase that acts in several distinct DNA metabolic pathways including DNA replication and recombination. To balance these functions and prevent unscheduled DNA degradation, Dna2 activities must be regulated. Here we show that Saccharomyces cerevisiae Dna2 function is controlled by sumoylation. We map the sumoylation sites to the N-terminal regulatory domain of Dna2 and show that in vitro sumoylation of recombinant Dna2 impairs its nuclease but not helicase activity. In cells, the total levels of the non-sumoylatable Dna2 variant are elevated. However, non-sumoylatable Dna2 shows impaired nuclear localization and reduced recruitment to foci upon DNA damage. Non-sumoylatable Dna2 reduces the rate of DNA end resection, as well as impedes cell growth and cell cycle progression through S phase. Taken together, these findings show that in addition to Dna2 phosphorylation described previously, Dna2 sumoylation is required for the homeostasis of the Dna2 protein function to promote genome stability.
ER  -

RANJHA, Lepakshi, Maryna LEVIKOVA, Veronika ALTMANNOVÁ, Lumír KREJČÍ a Petr CEJKA. Sumoylation regulates the stability and nuclease activity of Saccharomyces cerevisiae Dna2. \textit{COMMUNICATIONS BIOLOGY}. NEW YORK: NATURE PUBLISHING GROUP, 2019, roč.~2, MAY 8 2019, s.~1-12. ISSN~2399-3642. Dostupné z: https://dx.doi.org/10.1038/s42003-019-0428-0.

Podrobný výpis o publikaci