Budding yeast Hed1 down-regulates the mitotic recombination machinery when meiotic recombination is impaired

Abstract

In budding yeast, there are two RecA homologs: Rad51 and Dmc1. While Rad51 is involved in both mitotic and meiotic recombination, Dmc1 participates specifically in meiotic recombination. Here, we describe a meiosis-specific protein (Hed1) with a novel Rad51 regulatory function. Several observations indicate that Hed1 attenuates Rad51 activity when Dmc1 is absent. First, although double-strand breaks are normally poorly repaired in the dmc1 mutant, repair becomes efficient when Hed1 is absent, and this effect depends on Rad51. Second, Rad51 and Hed1 colocalize as foci on meiotic chromosomes, and chromosomal localization of Hed1 depends on Rad51. Third, production of Hed1 in vegetative cells inhibits Rad51-dependent recombination events. Fourth, the Hed1 protein shows an interaction with Rad51 in the yeast two-hybrid protein system. We propose that Hed1 provides a mechanism to ensure the coordinated action of Rad51 and Dmc1 during meiosis, by down-regulating Rad51 activity when Dmc1 is unavailable.[Keywords: Dmc1; Rad51; RecA homologs; crossing over; meiosis; recombination] Supplemental material is available at http://www.genesdev.org.

Red-Hed regulation: recombinase Rad51, though capable of playing the leading role, may be relegated to supporting Dmc1 in budding yeast meiosis: Figure 1.

“…Tsubouchi and Roeder's (2006) results also add to evidence indicating that Rad51 is capable of replacing Dmc1's function under certain circumstances. Here, we place these new findings in the context of previous observations and present a model to explain how Rad51 and Dmc1 may cooperate to promote interhomolog recombination in budding yeast, while at the same time accounting for the observed functional redundancy.…”

“…Red, Hop1, and Mek1 also influence the choice of recombination partner (as discussed in more detail below). In comparison to the axis-associated proteins, the properties reported for Hed1 indicate that it has a more direct and specific role in Rad51 inhibition (Tsubouchi and Roeder 2006). …”

“…The discovery that these two different recombinases are needed for normal levels of meiotic recombination in budding yeast raised the question of how the functions of these proteins relate to one another. The paper by Tsubouchi and Roeder (2006) in this issue of Genes & Development represents important progress toward what is apparently a rather complex answer. Tsubouchi and Roeder (2006) report discovery of a novel meiosis-specific protein, Hed1, which appears to inhibit Rad51 when Dmc1 is absent.…”

“…The paper by Tsubouchi and Roeder (2006) in this issue of Genes & Development represents important progress toward what is apparently a rather complex answer. Tsubouchi and Roeder (2006) report discovery of a novel meiosis-specific protein, Hed1, which appears to inhibit Rad51 when Dmc1 is absent. The authors show mutation of the HED1 gene allows cells to bypass the meiotic arrest caused by a dmc1 mutation and resolve meiosis-specific double-strand breaks (DSBs) using Rad51.…”

“…Red, Hop1, and Mek1 also influence the choice of recombination partner (as discussed in more detail below). In comparison to the axis-associated proteins, the properties reported for Hed1 indicate that it has a more direct and specific role in Rad51 inhibition (Tsubouchi and Roeder 2006). tional relative of RecA came from mutant analysis, detection of Rad51's DNA-dependent ATPase activity, and the observation that the protein forms right-handed helical filaments on DNA (Shinohara et al 1992;Ogawa et al 1993;Benson et al 1994).…”