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.

Basic information

Original name

Sumoylation regulates the stability and nuclease activity of Saccharomyces cerevisiae Dna2

Authors

RANJHA, Lepakshi (756 Switzerland), Maryna LEVIKOVA (756 Switzerland), Veronika ALTMANNOVÁ (203 Czech Republic, belonging to the institution), Lumír KREJČÍ (203 Czech Republic, belonging to the institution) and Petr CEJKA (guarantor)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.165

RIV identification code

RIV/00216224:14110/19:00108020

Organization unit

Faculty of Medicine

DOI

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

UT WoS

000467215700004

Keywords in English

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

Abstract

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.

Links

EF16_025/0007381, research and development project

Name: Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou

GA17-17720S, research and development project

Name: Vnitřní vlastnosti RAD51 vlákna a jeho biologické regulace

Investor: Czech Science Foundation

MUNI/A/1087/2018, interní kód MU

Name: Molekulární a buněčná biologie pro biomedicínské vědy

Investor: Masaryk University, Category A

206292/E/17/Z, interní kód MU

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

Investor: Wellcome Trust

Citovat

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

Detailed Information on Publication Record