Molecular characterization of Mre11-RAD50 proteins during Homologous Recombination Repair (HRR) in Toxoplasma gondii

TUROWSKI, VALERIA R.; RUIZ, DIEGO M.; ANGEL, SERGIO O.; SULLIVAN, WILLIAM JR.

Mar del Plata

Congreso; Reunión Anual de SOCIEDADES DE BIOCIENCIA SAIC SAFE SAB SAP AACYTAL NANOMED-ar HCS 2019; 2019

SOCIEDADES DE BIOCIENCIA SAIC SAFE SAB SAP AACYTAL NANOMED-ar HCS

The Homologous Recombination Repair (HRR) is critical to maintain the genome integrity during cell replication (late S / G2) but it has not been full elucidated in T. gondii. HRR starts with recognition of damaged DNA follow by generation of resection ends for which Mre11-RAD50-Nbs1 (MRN) complex is required. In our research group it was observed that genome of T. gondii encodes 50% of HRR proteins described in yeast and mammals suggesting either divergence between these homologues as the presence of parasite-specific components. In fact T. gondii harbours homologues of Mre11 and RAD50 proteins although no coding sequence relative to Nbs1 was found. In humans, MRN complex is composed by a homodimer of Mre11 with endo / exonuclease activity tethered to RAD50 ATPase homodimer and Nbs1.The Mre11 gene of T. gondii (TgMre11) contains an open reading frame encoding a polypeptide with 38.41% of identity to its human homologue and 535 residues longer. Superimposition among 3D-model of TgMre11 and HuMre11 crystal structure (RMS 0.84) showed three insertions of 20 amino acids each on relevant regions for both dimerization and interaction with other proteins or DNA. Thus, taking into account that Mre11 and RAD50 are predicted to be essential genes in T. gondii, disclosing structural-functional differences between these proteins and their human counterpart as well as characterize novel components of HRR in T. gondii might give insights about evolution of this pathway and help to identify novel drug targets.