The human Rad51 K133A mutant is functional for DNA double-strand break repair in human cells.

The human Rad51 K133A mutant is functional for DNA double-strand break repair in human cells. Research Abstract Details 

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The human Rad51 K133A mutant is functional for DNA double-strand break repair in human cells. Abstract Text:

Anthony L Forget,Matthew S Loftus,Dharia A McGrew,Brian T Bennett,Kendall L Knight,

The human Rad51 protein requires ATP for the catalysis of DNA strand exchange, as do all Rad51 and RecA-like recombinases. However, understanding the specific mechanistic requirements for ATP binding and hydrolysis has been complicated by the fact that ATP appears to have distinctly different effects on the functional properties of human Rad51 versus yeast Rad51 and bacterial RecA. Here we use RNAi methods to test the function of two ATP binding site mutants, K133R and K133A, in human cells. Unexpectedly, we find that the K133A mutant is functional for repair of DNA double-strand breaks when endogenous Rad51 is depleted. We also find that the K133A protein maintains wild-type-like DNA binding activity and interactions with Brca2 and Xrcc3, properties that undoubtedly promote its DNA repair capability in the cell-based assay used here. Although a Lys to Ala substitution in the Walker A motif is commonly assumed to prevent ATP binding, we show that the K133A protein binds ATP, but with an affinity approximately 100-fold lower than that of wild-type Rad51. Our data suggest that ATP binding and release without hydrolysis by the K133A protein act as a mechanistic surrogate in a catalytic process that applies to all RecA-like recombinases. ATP binding promotes assembly and stabilization of a catalytically active nucleoprotein filament, while ATP hydrolysis promotes filament disassembly and release from DNA.

The human Rad51 K133A mutant is functional for DNA double-strand break repair in human cells. Publishing Authors By Initials

AL Forget,MS Loftus,DA McGrew,BT Bennett,KL Knight,

For similar enzymes and coenzymes: enzymes: recombinases: rec a recombinases: rad51 recombinase research abstracts see: enzymes and coenzymes: enzymes: recombinases: rec a recombinases: rad51 recombinase research

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The human Rad51 K133A mutant is functional for DNA double-strand break repair in human cells. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Biochemistry

VOLUME: 46

Page Numbers: 3566-75

Journal Abbreviation: Biochemistry

ISSN: 0006-2960

DAY: 16

MONTH: 02

YEAR: 2007

The human Rad51 K133A mutant is functional for DNA double-strand break repair in human cells. Information

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LANGUAGE: eng

NlmUniqueID: 370623

The human Rad51 K133A mutant is functional for DNA double-strand break repair in human cells. Keywords Mesh Terms:

KEYWORDS: Rad51 Recombinase

MESH TERMS: physiology

Chemical & Substance for Abstract: The human Rad51 K133A mutant is functional for DNA double-strand break repair in human cells. Information

Substance Name: Rad51 Recombinase

Registry Number: EC 2.7.7.-

Grant and Affiliation Information for The human Rad51 K133A mutant is functional for DNA double-strand break repair in human cells.

AFFILIATION: Department of Biochemistry and Molecular Pharmacology, Aaron Lazare Research Building, 364 Plantation Street, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM44772

ACRONYM: GM

MEDLINETA: Biochemistry

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