Abstract
DNA double strand breaks(DSBs) are generated within genome DNA by exposure to ionizing radiation and certain chemicals. There are two pathways, in which DNA double strand breaks are rejoined, non-homologous end joining (NHEJ) and homologous recombination (HR). Ataxia telangiectasia like disorders (ATLD), characterized by hyper sensitivity to ionizing radiation(IR), immunodeficiency and an increased preposition to the development of malignancies, is phenotypically similar to ataxia telangiectasia (AT). hMRE11, the protein responsible of this disease, plays an important role in HR repair, and the N-terminal nuclease domain is widely conserved in eukaryote. hMRE11 forms the complex with NBS1 and hRAD50 and also function in miosis and S-phase checkpoint. Recently, it was reported that hMRE11 is methylated and phosphorylated, meaning of these modification in the DNA damage checkpoint response and DNA repair is unclear.
Therefore, we generated the several hMRE11 constructs mutated at methylation or phosphorylation sites and we investigated the role of HR repair using the DR-GFP reporter assay. Moreover, we also examine the effect of these hMRE11 modification on NBS1 by immunoprecipitation and immunofluorescence.
