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DNA repair

Gatekeepers of recombination

Nature volume 398, pages 665–667 (1999)Cite this article

Double-strand breaks on chromosomes may arise during DNA replication, by enzymatic cleavage, or from ionizing radiation. This damage can be repaired in several ways. The two broken ends may simply be stuck back together by a process called nonhomologous end-joining, or the break may be repaired through genetic exchange with a homologous chromosome (homologous recombination). How do cells choose which pathway to use? On page 728 of this issue, Van Dyck et al.1 suggest that the Rad52 protein may play the role of ‘gatekeeper’ in homologous recombination, just as the Ku proteins seem to do for nonhomologous end-joining.

So far as we can tell, the basic features of recombination are conserved from bacteria, through yeast, to humans. The key step — that of strand exchange, when the 3′ end invades the donor duplex — is carried out within a filament of Rad51, whose bacterial homologue is RecA5. Rad52 seems to occur only in eukaryotes. But surprisingly, in Saccharomyces at least, it is the key protein for recombination. Almost all homologous recombination, whether spontaneous or induced by double-strand breaks, is eliminated in yeast rad52 mutants. Curiously, Rad51-deficient cells can still carry out several types of homologous recombination and repair, including those initiated by double-strand breaks6,7. The situation is not yet clear for higher eukaryotes. In vertebrates, a lack of Rad52 is not nearly as serious as the absence of Rad51, which is lethal8. Possibly a Rad52 homologue will be found. On the other hand, the apparent absence of a Rad52 homologue in the completely sequenced nematode genome should make us pause in our quest for some unity of mechanism (although I will take modest wagers that such a gene may yet turn up).

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Figure 1: Alternative pathways of double-strand break repair.

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  1. Rosenstiel Center and the Department of Biology, Brandeis University, MS029, Waltham, 02454-9110, Massachusetts, USA

    James E. Haber

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Haber, J. Gatekeepers of recombination. Nature 398, 665–667 (1999). https://doi.org/10.1038/19423

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