Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Sumoylation of the Rad1 nuclease promotes DNA repair and regulates its DNA association

P. Sarangi, Z. Bartosova, V. Altmannova, C. Holland, M. Chavdarova, SE. Lee, L. Krejci, X. Zhao,

. 2014 ; 42 (10) : 6393-404.

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc14074231

The Saccharomyces cerevisiae Rad1-Rad10 complex is a conserved, structure-specific endonuclease important for repairing multiple types of DNA lesions. Upon recruitment to lesion sites, Rad1-Rad10 removes damaged sequences, enabling subsequent gap filling and ligation. Acting at mid-steps of repair, the association and dissociation of Rad1-Rad10 with DNA can influence repair efficiency. We show that genotoxin-enhanced Rad1 sumoylation occurs after the nuclease is recruited to lesion sites. A single lysine outside Rad1's nuclease and Rad10-binding domains is sumoylated in vivo and in vitro. Mutation of this site to arginine abolishes Rad1 sumoylation and impairs Rad1-mediated repair at high doses of DNA damage, but sustains the repair of a single double-stranded break. The timing of Rad1 sumoylation and the phenotype bias toward high lesion loads point to a post-incision role for sumoylation, possibly affecting Rad1 dissociation from DNA. Indeed, biochemical examination shows that sumoylation of Rad1 decreases the complex's affinity for DNA without affecting other protein properties. These findings suggest a model whereby sumoylation of Rad1 promotes its disengagement from DNA after nuclease cleavage, allowing it to efficiently attend to large numbers of DNA lesions.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc14074231
003      
CZ-PrNML
005      
20141006123212.0
007      
ta
008      
141006s2014 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1093/nar/gku300 $2 doi
035    __
$a (PubMed)24753409
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Sarangi, Prabha $u Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA Programs in Biochemistry, Cell, and Molecular Biology, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA.
245    10
$a Sumoylation of the Rad1 nuclease promotes DNA repair and regulates its DNA association / $c P. Sarangi, Z. Bartosova, V. Altmannova, C. Holland, M. Chavdarova, SE. Lee, L. Krejci, X. Zhao,
520    9_
$a The Saccharomyces cerevisiae Rad1-Rad10 complex is a conserved, structure-specific endonuclease important for repairing multiple types of DNA lesions. Upon recruitment to lesion sites, Rad1-Rad10 removes damaged sequences, enabling subsequent gap filling and ligation. Acting at mid-steps of repair, the association and dissociation of Rad1-Rad10 with DNA can influence repair efficiency. We show that genotoxin-enhanced Rad1 sumoylation occurs after the nuclease is recruited to lesion sites. A single lysine outside Rad1's nuclease and Rad10-binding domains is sumoylated in vivo and in vitro. Mutation of this site to arginine abolishes Rad1 sumoylation and impairs Rad1-mediated repair at high doses of DNA damage, but sustains the repair of a single double-stranded break. The timing of Rad1 sumoylation and the phenotype bias toward high lesion loads point to a post-incision role for sumoylation, possibly affecting Rad1 dissociation from DNA. Indeed, biochemical examination shows that sumoylation of Rad1 decreases the complex's affinity for DNA without affecting other protein properties. These findings suggest a model whereby sumoylation of Rad1 promotes its disengagement from DNA after nuclease cleavage, allowing it to efficiently attend to large numbers of DNA lesions.
650    _2
$a DNA $x metabolismus $7 D004247
650    _2
$a poškození DNA $7 D004249
650    12
$a oprava DNA $7 D004260
650    _2
$a enzymy opravy DNA $x chemie $x genetika $x metabolismus $7 D045643
650    _2
$a endonukleasy $x chemie $x genetika $x metabolismus $7 D004720
650    _2
$a intracelulární signální peptidy a proteiny $x fyziologie $7 D047908
650    _2
$a lysin $x metabolismus $7 D008239
650    _2
$a mutace $7 D009154
650    _2
$a protein-serin-threoninkinasy $x fyziologie $7 D017346
650    _2
$a Saccharomyces cerevisiae - proteiny $x chemie $x genetika $x metabolismus $x fyziologie $7 D029701
650    12
$a sumoylace $7 D058207
650    _2
$a ubikvitinligasy $x fyziologie $7 D044767
655    _2
$a časopisecké články $7 D016428
655    _2
$a Research Support, N.I.H., Extramural $7 D052061
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Bartosova, Zdenka $u Department of Biology, Masaryk University, Brno 62500, Czech Republic.
700    1_
$a Altmannová, Veronika $u Department of Biology, Masaryk University, Brno 62500, Czech Republic. $7 mub2011626283
700    1_
$a Holland, Cory $u Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
700    1_
$a Chavdarova, Melita $u National Centre for Biomolecular Research, Masaryk University, Brno 62500, Czech Republic.
700    1_
$a Lee, Sang Eun $u Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA Division of Radiation Biology, Department of Radiation Oncology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
700    1_
$a Krejci, Lumir $u Department of Biology, Masaryk University, Brno 62500, Czech Republic National Centre for Biomolecular Research, Masaryk University, Brno 62500, Czech Republic International Clinical Research Center, St. Anne's University Hospital in Brno, Brno 60200, Czech Republic.
700    1_
$a Zhao, Xiaolan $u Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA zhaox1@mskcc.org.
773    0_
$w MED00003554 $t Nucleic acids research $x 1362-4962 $g Roč. 42, č. 10 (2014), s. 6393-404
856    41
$u https://pubmed.ncbi.nlm.nih.gov/24753409 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20141006 $b ABA008
991    __
$a 20141006123649 $b ABA008
999    __
$a ok $b bmc $g 1042114 $s 873143
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2014 $b 42 $c 10 $d 6393-404 $i 1362-4962 $m Nucleic acids research $n Nucleic Acids Res $x MED00003554
LZP    __
$a Pubmed-20141006

Najít záznam

Citační ukazatele

Možnosti archivace