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Vol. 16, Issue 12, 5804-5818, December 2005
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* Department of Biochemistry and Cell Biology, State University of New York at Stony Brook, Stony Brook, NY 11794-5215;
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030; and
Department of Chromosome Research, University of Vienna, A-1030 Vienna, Austria
Submitted May 31, 2005;
Revised September 26, 2005;
Accepted September 29, 2005
Monitoring Editor: Orna Cohen-Fix
Meiotic recombination differs from mitotic recombination in that DSBs are repaired using homologous chromosomes, rather than sister chromatids. This change in partner choice is due in part to a barrier to sister chromatid repair (BSCR) created by the meiosis-specific kinase, Mek1, in a complex with two other meiosis-specific proteins, Hop1 and Red1. HOP1 contains two functional domains, called the N and C domains. Analysis of a point mutation that specifically inactivates the C domain (hop1-K593A) reveals that the N domain is sufficient for Hop1 localization to chromosomes and for Red1 and Hop1 interactions. The C domain is needed for spore viability, for chromosome synapsis, and for preventing DMC1-independent DSB repair, indicating it plays a role in the BSCR. All of the hop1-K593A phenotypes can be bypassed by fusion of ectopic dimerization domains to Mek1, suggesting that the function of the C domain is to promote Mek1 dimerization. Hop1 is a DSB-dependent phosphoprotein, whose phosphorylation requires the presence of the C domain, but is independent of MEK1. These results suggest a model in which Hop1 phosphorylation in response to DSBs triggers dimerization of Mek1 via the Hop1 C domain, thereby enabling Mek1 to phosphorylate target proteins that prevent repair of DSBs by sister chromatids.
Abbreviations used: BSCR, barrier to sister chromatid repair; DSB, double-strand break; AE, axial element; SC, synaptonemal complex.
These authors contributed equally to this work.
Address correspondence to: Nancy M. Hollingsworth (nhollin{at}ms.cc.sunysb.edu).
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