Effect of amino acid substitutions in the rad50 ATP binding
domain on DNA double strand break repair in yeast.

J 2005

Effect of amino acid substitutions in the rad50 ATP binding domain on DNA double strand break repair in yeast.

CHEN, ling, Kelly TRUJILLO, Stephen VAN KOMEN, Dong ROH, Lumír KREJČÍ et. al.

Základní údaje

Originální název

Effect of amino acid substitutions in the rad50 ATP binding domain on DNA double strand break repair in yeast.

Název česky

Vliv aminokyselinových substitucí v ATP vazebné doméně proteinu Rad50

Autoři

CHEN, ling (840 Spojené státy), Kelly TRUJILLO (840 Spojené státy), Stephen VAN KOMEN (840 Spojené státy), Dong ROH (410 Korejská republika), Lumír KREJČÍ (203 Česká republika, garant), Kevin LEWIS (840 Spojené státy), Mike RESNICK (840 Spojené státy), Patrick SUNG (840 Spojené státy) a Alan TOMKINSON (840 Spojené státy)

Vydání

Journal of Biological Chemistry, Bethesda, USA, Amer. Soc. Biochem. Mol. Biol. 2005, 0021-9258

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10600 1.6 Biological sciences

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.854

Organizační jednotka

Přírodovědecká fakulta

UT WoS

000226449100031

Klíčová slova anglicky

Rad50; ATPase; repair;

Štítky

ATPase, Rad50, repair

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 15. 5. 2009 22:53, doc. Mgr. Lumír Krejčí, Ph.D.

Anotace

ORIG CZ

V originále

The Saccharomyces cerevisiae Rad50-Mre11-Xrs2 complex plays a central role in the cellular response to DNA double strand breaks. Rad50 has a globular ATPase head domain with a long coiled-coil tail. DNA binding by Rad50 is ATP-dependent and the Rad50-Mre11-Xrs2 complex possesses DNA unwinding and endonuclease activities that are regulated by ATP. Here we have examined the role of the Rad50 Walker type A ATP binding motif in DNA double strand break repair by a combination of genetic and biochemical approaches. Replacement of the conserved lysine residue within the Walker A motif with alanine, glutamate, or arginine results in the same DNA damage sensitivity and homologous recombination defect as the rad50 deletion mutation. The Walker A mutations also cause a deficiency in non-homologous end-joining. As expected, complexes containing the rad50 Walker A mutant proteins are defective in ATPase, ATP-dependent DNA unwinding, and ATP-stimulated endonuclease activities. Although the DNA end-bridging activity of the Rad50-Mre11-Xrs2 complex is ATP-independent, the end-bridging activity of complexes containing the rad50 Walker A mutant proteins is salt-sensitive. These results provide a molecular explanation for the observed in vivo defects of the rad50 Walker mutant strains and reveal a novel ATP-independent function for Rad50 in DNA end-bridging.

Česky

Vliv ATP na funkci Rad50 proteinu

Citovat

CHEN, ling, Kelly TRUJILLO, Stephen VAN KOMEN, Dong ROH, Lumír KREJČÍ, Kevin LEWIS, Mike RESNICK, Patrick SUNG a Alan TOMKINSON. Effect of amino acid substitutions in the rad50 ATP binding domain on DNA double strand break repair in yeast. Journal of Biological Chemistry. Bethesda, USA: Amer. Soc. Biochem. Mol. Biol., 2005, roč. 280, č. 4, s. 2620-7, 7 s. ISSN 0021-9258.

@article{708606,
   author = {Chen, ling and Trujillo, Kelly and Van Komen, Stephen and Roh, Dong and Krejčí, Lumír and Lewis, Kevin and Resnick, Mike and Sung, Patrick and Tomkinson, Alan},
   article_location = {Bethesda, USA},
   article_number = {4},
   keywords = {Rad50; ATPase; repair;},
   language = {eng},
   issn = {0021-9258},
   journal = {Journal of Biological Chemistry},
   title = {Effect of amino acid substitutions in the rad50 ATP binding domain on DNA double strand break repair in yeast.},
   url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15546877&query_hl=20&itool=pubmed_docsum},
   volume = {280},
   year = {2005}
}

TY  - JOUR
ID  - 708606
AU  - Chen, ling - Trujillo, Kelly - Van Komen, Stephen - Roh, Dong - Krejčí, Lumír - Lewis, Kevin - Resnick, Mike - Sung, Patrick - Tomkinson, Alan
PY  - 2005
TI  - Effect of amino acid substitutions in the rad50 ATP binding domain on DNA double strand break repair in yeast.
JF  - Journal of Biological Chemistry
VL  - 280
IS  - 4
SP  - 2620-7
EP  - 2620-7
PB  - Amer. Soc. Biochem. Mol. Biol.
SN  - 00219258
KW  - Rad50
KW  - ATPase
KW  - repair;
UR  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15546877&query_hl=20&itool=pubmed_docsum
L2  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15546877&query_hl=20&itool=pubmed_docsum
N2  - The Saccharomyces cerevisiae Rad50-Mre11-Xrs2 complex plays a central role in the cellular response to DNA double strand breaks. Rad50 has a globular ATPase head domain with a long coiled-coil tail. DNA binding by Rad50 is ATP-dependent and the Rad50-Mre11-Xrs2 complex possesses DNA unwinding and endonuclease activities that are regulated by ATP. Here we have examined the role of the Rad50 Walker type A ATP binding motif in DNA double strand break repair by a combination of genetic and biochemical approaches. Replacement of the conserved lysine residue within the Walker A motif with alanine, glutamate, or arginine results in the same DNA damage sensitivity and homologous recombination defect as the rad50 deletion mutation. The Walker A mutations also cause a deficiency in non-homologous end-joining. As expected, complexes containing the rad50 Walker A mutant proteins are defective in ATPase, ATP-dependent DNA unwinding, and ATP-stimulated endonuclease activities. Although the DNA end-bridging activity of the Rad50-Mre11-Xrs2 complex is ATP-independent, the end-bridging activity of complexes containing the rad50 Walker A mutant proteins is salt-sensitive. These results provide a molecular explanation for the observed in vivo defects of the rad50 Walker mutant strains and reveal a novel ATP-independent function for Rad50 in DNA end-bridging.
ER  -

CHEN, ling, Kelly TRUJILLO, Stephen VAN KOMEN, Dong ROH, Lumír KREJČÍ, Kevin LEWIS, Mike RESNICK, Patrick SUNG a Alan TOMKINSON. Effect of amino acid substitutions in the rad50 ATP binding domain on DNA double strand break repair in yeast. \textit{Journal of Biological Chemistry}. Bethesda, USA: Amer. Soc. Biochem. Mol. Biol., 2005, roč.~280, č.~4, s.~2620-7, 7 s. ISSN~0021-9258.

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