HES1 (Hes family bHLH transcription factor 1) is a repressor of genes that require a bHLH protein for their transcription. It acts to negatively regulate myogenesis by inhibiting the functions of MYOD1 and ASH1. HES1 binds DNA on N-box motifs such as 5'-CACNAG-3' with high affinity and on E-box motifs such as 5'-CANNTG-3' with low affinity. It may play a role in a functional FA core complex response to DNA cross-link damage, is required for the stability and nuclear localization of FA core complex proteins, as well as for FANCD2 mono-ubiquitination in response to DNA damage. It has been implicated in cell differentiation, cell cycle arrest and apoptosis, and metastasis in cancer. It is expressed in the nucleus of a variety of tissues. References: Cancer Biol Ther. 2015 Mar; 16(3): 353–359