Human Rad52-mediated homology search and annealing occurs by continuous interactions between overlapping nucleoprotein complexes

Eli Rothenberg; Jill M Grimme; Maria Spies; Taekjip Ha

doi:10.1073/pnas.0810317106

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Human Rad52-mediated homology search and annealing occurs by continuous interactions between overlapping nucleoprotein complexes

Journal article

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Human Rad52-mediated homology search and annealing occurs by continuous interactions between overlapping nucleoprotein complexes

Eli Rothenberg, Jill M Grimme, Maria Spies and Taekjip Ha

Proceedings of the National Academy of Sciences - PNAS, Vol.105(51), pp.20274-20279

12/23/2008

DOI: 10.1073/pnas.0810317106

PMCID: PMC2629295

PMID: 19074292

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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.

Biological Sciences

FRET

single-molecule

DNA recombination

DNA repair

fluorescence microscopy

Details

Title: Subtitle: Human Rad52-mediated homology search and annealing occurs by continuous interactions between overlapping nucleoprotein complexes
Creators: Eli Rothenberg - Howard Hughes Medical Institute and Center for the Physics of Living Cells
Jill M Grimme - Departments of
Maria Spies - Departments of
Taekjip Ha - Howard Hughes Medical Institute and Center for the Physics of Living Cells
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.105(51), pp.20274-20279
DOI: 10.1073/pnas.0810317106
PMID: 19074292
PMCID: PMC2629295
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 12/23/2008
Academic Unit: Radiation Oncology; Biochemistry and Molecular Biology
Record Identifier: 9984025299102771

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