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© The Rockefeller University Press, 0021-9525/1999//11 $5.00
The Journal of Cell Biology, Volume 144, Number 1, , 1999 11-20

Article

Sequestration of Mammalian Rad51-Recombination Protein into Micronuclei



Thomas Haaf*, Elke Raderschall*, Gurucharan Reddy{ddagger}, David C. Ward§, Charles M. Radding§, and Efim I. Golub§

* Max-Planck-Institute of Molecular Genetics, 14195 Berlin, Germany; {ddagger} Pangene Corporation, Menlo Park, California 94025; and § Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06520

The mammalian Rad51 protein is involved in homologous recombination and in DNA damage repair. Its nuclear distribution after DNA damage is highly dynamic, and distinct foci of Rad51 protein, distributed throughout the nuclear volume, are induced within a few hours after {gamma} irradiation; these foci then coalesce into larger clusters. Rad51-positive cells do not undergo DNA replication. Rad51 foci colocalize with both replication protein A and sites of unscheduled DNA repair synthesis and may represent a nuclear domain for recombinational DNA repair. By 24 h postirradiation, most foci are sequestered into micronuclei or assembled into Rad51-coated DNA fibers. These micronuclei and DNA fibers display genome fragmentation typical of apoptotic cell death. Other repair proteins, such as Rad52 and Gadd45, are not eliminated from the nucleus. DNA double strand breaks in repair-deficient cells or induced by the clastogen etoposide are also accompanied by the sequestering of Rad51 protein before cell death. The spindle poison colcemid causes cell cycle arrest and Rad51-foci formation without directly damaging DNA. Collectively, these observations suggest that mammalian Rad51 protein associates with damaged DNA and/or with DNA that is temporarily or irreversibly unable to replicate and these foci may subsequently be eliminated from the nucleus.

Key Words: DNA repair • immunofluorescence • micronuclei • Rad51 • repairosome

Abbreviations used in this paper: BrdU, 5-bromodeoxyuridine; 60Co, cobalt 60; 137Cs, cesium 137; DAPI, 4',6-diamidino-2-phenylindole; DSB, double strand break; FISEL, fluorescence in situ end labeling; MN, micronuclei; RNAPII, RNA polymerase II; RPA, replication protein A; ss, single strand; XP, Xerodema pigmentosum.


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