The Role Of DNA Helicase HELQ On Cell Proliferation Regulation

DNA interstrand crosslinks（ICL）is a very serious DNA damage that blocks DNA replication and transcription.In recent years,there have been a therapeutic treatment for cancer by the inhibition of cell cycle test points and the activity of DNA damage repair related protein,combined with chemotherapy drugs.HELQ is a DNA helicase involved in ICL repair,and its repair pathway is parallel to the FA signaling pathway.Therefore,this study will provide more selective and theoretical guidance for cancer treatment.HELQ mutant mice exhibits low fertility,testicular and ovarian atrophy,only support cells in some tubules,ovarian and pituitary easily tumor predisposition.Our previous study showed that the lack of DNA helicase HELQ led to significantly low efficiency of the primordial germ cells（mPGCLCs）differentiated from mouse embryonic stem cell.However,it did not affect the maintenance of pluripotency of mouse embryonic stem cells.Helq^-/-mES was able to pass the tetraploid compensation experiment,and there was no significant difference between EpiLCs differentiated from wild type and Helq^-/-mES.Firstly,to investigate how the DNA helicase HELQ affects the differentiation of PGCLCs,we counted the number of EBs at the time of differentiation of PGCLCs,and it is found that there was no significant difference in the number of cells at second and fourth day between wild type and Helq^-/-,while it became different on the sixth day,indicating that HELQ did affect the maintenance of germ cells.In addition,Hela and human embryonic stem cells were used to further analyze whether HELQ had the same function in other cell lines.The HELQ mutate cell lines were obtained by CRISPR-Cas9technique.Cell apoptosis and cell cycle of HELQ^-/-Hela cell line were analysed after treatment with MMC.It showed that severe G2/M phase arrest was observed in the Hela mutan cell lines and the ratio of cell apoptosis in mutant cell line was significantly higher than wild type at 24h after MMC treatment.However,the cell cycle of HELQ^-/-human embryonic stem cell（hES）were no different from wild type after MMC treatment.Moreover,by real-time qPCR,it showed no significant difference between wild type and mutant hES in the expression of pluripotency markers.To sum up,DNA helicase HELQ functions mainly by participating in the regulation of cell cycle and cell apoptosis,and different impact on different cell lines may be related to its tissue-specific expression.