Dss1 regulates interaction of Brh2 with DNA.
Brh2, the BRCA2 homologue in Ustilago maydis, plays a crucial role in homologous recombination by controlling Rad51. In turn, Brh2 is governed by Dss1, an intrinsically disordered protein that forms a tight complex with the C-terminal region of Brh2. This region of the protein associating with Dss1 is highly conserved in sequence and by comparison with mammalian BRCA2 corresponds to a part of the DNA binding domain with characteristic OB folds. The N-terminal region of Brh2 harbors a less-defined but powerful DNA binding site, the activity of which is revealed upon deletion of the C-terminal region. Full-length Brh2 complexed with Dss1 binds DNA slowly, while the N-terminal fragment binds quickly. The DNA binding activity of full-length Brh2 appears to correlate with dissociation of Dss1. Addition of Dss1 to the heterotypic Brh2-Dss1 complex attenuates DNA binding activity, but not by direct competition for the N-terminal DNA binding site. Conversely, the Brh2-Dss1 complex dissociates more quickly when DNA is present. These findings suggest a model in which binding of Brh2 to DNA is subject to allosteric regulation by Dss1.
Zhou
Qingwen
Q
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York 10065, USA.
Mazloum
Nayef
N
Mao
Ninghui
N
Kojic
Milorad
M
Holloman
William K
WK
D024682:BRCA2 Protein / Q000737:chemistry; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D014588:Ustilago / Q000235:genetics*
D024682:BRCA2 Protein; C106711:BRCA2 protein, mouse; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D010446:Peptide Fragments; D051135:Rad51 Recombinase