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Brh2, the BRCA2 ortholog in Ustilago maydis, enables recombinational repair of DNA by controlling Rad51 and is in turn regulated by Dss1. Interplay with Rad51 is conducted via the BRC element located in the N-terminal region of the protein and through an unrelated domain, CRE, at the C terminus. Mutation in either BRC or CRE severely reduces functional activity, but repair deficiency of the brh2 mutant can be complemented by expressing BRC and CRE on different molecules. This intermolecular complementation is dependent upon the presence of Dss1. Brh2 molecules associate through the region overlapping with the Dss1-interacting domain to form at least dimer-sized complexes, which in turn, can be dissociated by Dss1 to monomer. We propose that cooperation between BRC and CRE domains and the Dss1-provoked dissociation of Brh2 complexes are requisite features of Brh2's molecular mechanism.Accumulating evidence points to a choreographed interaction between Rad51 and BRCA2 as a critical mechanism governing recombinational repair (9,21,27,30). Proper regulation of the repair process requires assembly of Rad51 into its catalytically active form, the nucleoprotein filament. This filament is generated through Rad51's polymerization on singlestranded DNA, a process that appears to be mediated by BRCA2. Biochemical analyses using Brh2, the BRCA2-related protein from Ustilago maydis, have demonstrated that it nucleates Rad51 assembly at the site of a double-strand/singlestrand DNA junction, the prerequisite structure for recombinational repair arising from resection of a double-strand DNA end to reveal a protruding 3Ј single-stranded tail (32). However, molecular genetic experimentation with U. maydis (15) as well as biochemical studies using peptides modeling BRC elements from the human BRCA2 (6) or a polypeptide containing multiple BRC elements (26) suggest a role for BRCA2 in organization or stabilization of Rad51 filaments.Regulated assembly of the filament may be balanced on the one hand by interaction of Rad51 with BRC elements and on the other hand by some interplay with a second domain located at the extreme C terminus of BRCA2 (CRE [C-terminal Rad51-interacting element]; see below) (4). The BRC domain comprises eight reiterated sequences of about 30 amino acids each whose structures have been proposed to mimic an element in Rad51 that provides a critical determinant at the polymerization interface, gluing Rad51 molecules into a chain (20,25). Rad51 interaction with the C-terminal domain appears to be controlled by phosphorylation of a key BRCA2 residue that is targeted by cyclin-dependent kinases (4). Proper Rad51 filament assembly at DNA sites of repair requires a precisely coordinated interplay between BRCA2's Rad51-interacting domains and its DSS1/DNA-binding domain (DBD). The latter (31) consists of a tandem array of OB (oligonucleotide/oligosaccharide-binding) folds, with a double-helical tower emerging from one OB fold topped by a helix-turn-helix, and a helical domain that is laced to the adjacent OB folds by ...

The strong association of both the mild and severe types of allopurinol cADRs with the HLA-B*58:01 allele were observed. The results indicated that the prospective use of a genetic test of HLA-B*58:01 might reduce the prevalence of allopurinol-induced cADRs. Original submitted 7 March 2012; Revision submitted 21 May 2012.

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