Two RecA homologs have been identified in Ustilago mavids. One is orthologous to Rad5 I while the other is a structurally divergent protein encoded by the REC2 gene. Both are necessary for proficiency in the repair of DNA damage, meiotic and mitotic recombination, and maintenance of the genetic Integrity of the organism. Biochemical evidence indicates that Rec2 performs the catalytic function of homologous pairing and DNA strand exchange more effectively than Rad51 These findings challenge the current dogma established in studies using yeast and human systems that feature Rad5 1 as the central catalytic component of a double-strand-break-repair complex. In this proposal we seek to understand the relationship between Rec2 and Rad51 We also plan to investigate the relationship of Rec2 and Rad 51 with Brh2 a newly discovered homolog of BRCA2, the product of a human breast cancer gene. The BRH2 gene was identified in a mutant screen for DNA repair deficiency.
Three aims are proposed. First, we will study interaction between Rec2 and Rad5 1 in promoting several homologous pairing and strand transfer reactions. Second, we will investigate the BRH2 gene and examine its genetic and biochemical interactions with REC2 and RAD5I. Third. We have discovered a novel mode of plasmid replication in U. mavdis that appears to depend upon REC2 gene function and posttranscriptional gene silencing, and plan several experiments to establish these relationships in a definitive manner. We believe that the studies proposed here will provide novel insight into the basis of homologous pairing processes and provide new insight into the function of a gene important in human breast cancer.
| de Sena-Tomás, Carmen; Yu, Eun Young; Calzada, Arturo et al. (2015) Fungal Ku prevents permanent cell cycle arrest by suppressing DNA damage signaling at telomeres. Nucleic Acids Res 43:2138-51 |
| de Sena-Tomás, Carmen; Sutherland, Jeanette H; Milisavljevic, Mira et al. (2015) LAMMER kinase contributes to genome stability in Ustilago maydis. DNA Repair (Amst) 33:70-7 |
| Zhou, Qingwen; Holloman, William K (2014) Dual DNA-binding domains shape the interaction of Brh2 with DNA. DNA Repair (Amst) 22:104-11 |
| Kojic, Milorad; Sutherland, Jeanette H; Pérez-Martín, José et al. (2013) Initiation of meiotic recombination in Ustilago maydis. Genetics 195:1231-40 |
| Yu, Eun Young; Kojic, Milorad; Holloman, William K et al. (2013) Brh2 and Rad51 promote telomere maintenance in Ustilago maydis, a new model system of DNA repair proteins at telomeres. DNA Repair (Amst) 12:472-9 |
| Kojic, Milorad; Holloman, William K (2012) Brh2 domain function distinguished by differential cellular responses to DNA damage and replication stress. Mol Microbiol 83:351-61 |
| Zhou, Qingwen; Kojic, Milorad; Holloman, William K (2012) Dss1 release activates DNA binding potential in Brh2. Biochemistry 51:9137-46 |
| Holloman, William K (2011) Unraveling the mechanism of BRCA2 in homologous recombination. Nat Struct Mol Biol 18:748-54 |
| Kojic, Milorad; Zhou, Qingwen; Fan, Jie et al. (2011) Mutational analysis of Brh2 reveals requirements for compensating mediator functions. Mol Microbiol 79:180-91 |
| de Sena-Tomás, Carmen; Fernández-Álvarez, Alfonso; Holloman, William K et al. (2011) The DNA damage response signaling cascade regulates proliferation of the phytopathogenic fungus Ustilago maydis in planta. Plant Cell 23:1654-65 |
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