Deciphering the role of human MSL2 and MSL1 within and beyond the MSL complex

Abstract

While the components of the MSL (Male Specific Lethal) complex in Drosophila are well studied and known to play a critical role in dosage compensation, there is little known about the function of its evolutionary conserved human orthologues. To better understand how the MSL complex is involved in cellular processes this study focuses on two subunits, MSL2 and MSL1. To decipher the function of human MSL2 and MSL1 within the MSL complex a loss-of-function approach was chosen using the CRISPR/Cas9 genome editing method. Based on previous findings further characterization of these proteins in the DNA damage response was performed. Using immunofluorescence microscopy perturbed 53BP1 nuclear body formation was observed in cells lacking either MSL2 or MSL1 and a possible role in replication related DNA damage was studied as well. Using a modified proximity biotin ligation based BioID approach novel interactors and possible substrates of the E3 ubiquitin ligase MSL2 were also identified.