Human Rad52-mediated Homology Search and Annealing Occurs by Continuous Interactions Between Overlapping Nucleoprotein Complexes

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2008 Dec 17

PMID 19074292

Citations 70

Authors

Eli Rothenberg

Jill M Grimme

Maria Spies

Taekjip Ha

Affiliations

Soon will be listed here.

Abstract

The Rad52 protein has critical functions in distinct pathways of the homology-directed DNA repair, one of which is to promote the annealing of complementary strands of DNA. Both yeast and human Rad52 proteins organize into ring-shaped oligomers with the predominant form being a heptamer. Despite the wealth of information obtained in previous investigations, how Rad52 mediates homology search and annealing remains unclear. Here, we developed single-molecule fluorescence resonance energy transfer approaches to probe hRad52-mediated DNA annealing events in real time. We found that annealing proceeds in successive steps involving rearrangements of the ssDNA-hRad52 complex. Moreover, after initial pairing, further search for extended homology occurs without dissociation. This search process is driven by an interaction between 2 overlapping nucleoprotein complexes. In light of these observations we propose a model for hRad52-mediated DNA annealing where ssDNA release and dsDNA zippering are coordinated through successive rearrangement of overlapping nucleoprotein complexes.

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