Conformational changes modulate the activity of human RAD51 protein.

Détails

ID Serval
serval:BIB_D0CF740EFC46
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Conformational changes modulate the activity of human RAD51 protein.
Périodique
Journal of Molecular Biology
Auteur(s)
Liu Y., Stasiak A.Z., Masson J.Y., McIlwraith M.J., Stasiak A., West S.C.
ISSN
0022-2836[print], 0022-2836[linking]
Statut éditorial
Publié
Date de publication
2004
Peer-reviewed
Oui
Volume
337
Numéro
4
Pages
817-827
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Homologous recombination provides a major pathway for the repair of DNA double-strand breaks in mammalian cells. Defects in homologous recombination can lead to high levels of chromosomal translocations or deletions, which may promote cell transformation and cancer development. A key component of this process is RAD51. In comparison to RecA, the bacterial homologue, human RAD51 protein exhibits low-level strand-exchange activity in vitro. This activity can, however, be stimulated by the presence of high salt. Here, we have investigated the mechanistic basis for this stimulation. We show that high ionic strength favours the co-aggregation of RAD51-single-stranded DNA (ssDNA) nucleoprotein filaments with naked duplex DNA, to form a complex in which the search for homologous sequences takes place. High ionic strength allows differential binding of RAD51 to ssDNA and double-stranded DNA (dsDNA), such that ssDNA-RAD51 interactions are unaffected, whereas those between RAD51 and dsDNA are destabilized. Most importantly, high salt induces a conformational change in RAD51, leading to the formation of extended nucleoprotein filaments on ssDNA. These extended filaments mimic the active form of the Escherichia coli RecA-ssDNA filament that exhibits efficient strand-exchange activity.
Mots-clé
DNA/metabolism, DNA, Single-Stranded/metabolism, DNA-Binding Proteins/metabolism, Humans, Osmolar Concentration, Protein Binding, Protein Conformation, Rad51 Recombinase
Pubmed
Web of science
Création de la notice
24/01/2008 11:36
Dernière modification de la notice
20/08/2019 16:51
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