Abstract
DNA double-strand breaks (DSB) are a serious damage, which can lead to genomic instability and/or cell death. However, mammalian cells are able to immediately recognize and repair DSBs, once they are generated in the genomic DNA. Since genomic DNA is compacted into chromatin structure together with histone proteins, in higher eukaryotic cells, this structure might be remodeled to recognize and repair the damaged DNA site, with specific modifications of histones.
It has been shown in the budding yeast , S. cerevisiae, that histone H2B is ubiquitinated by Bre1 E3 ubiquitin ligase, and it is required for cell cycle checkpoint and DNA repair. However, the function of RNF20, the human homolog of Yeast BRE1, as well as H2B monoubuquitination by it, in DNA damage response, is poorly understood.
Herein, it was found that H2B monoubiquitination by RNF20 is important for DNA repair. Reduction of RNF20 by RNAi showed MMC and IR sensitivity.
Yeast two hybrids experiment showed the direct binding of RNF20 with NBS1. This is confirmed by observation that RNF20 is present in immunoprecipitates from cell extracts with NBS1. These result indicated that ubiquitination of histone H2B by RNF20 is required for Homologous recombination after exposure to IR.
