The Study On The Role And Mechanism Of CtIP In DNA Double Strand Break Repair

The genomeofeukaryotic carries on almostall message about survival and development of organism,it is crucial for eukaryotic to complete normal vital movement.However,the safety of genome DNA cannot obtain completely guarantee.The metabolism by-products from intracellular the radiation from extracellular and drug stimulation will all induce the damage of genome DNA.If the genome DNA have been damaged but failure to get timely and correct repair,it will cause a serious genetic mutation or even cancer.DNA double-strand breaks(DSBs)is themost serious damage type for genome DNA.In order to deal with the damage correctly,the organism have evolved two major mechanismsit is non-homologous end-joining(NHEJ)and homologous recombination(HR).CtIP was initially identified as a co-factors of transcription.Recently,it has been gradually proved that it has close tied to the occurrence and development of tumor,genomic instability and initial resection of DSBs repair.However,the complete mechanism of molecule CtIP in the process of DSBs repair is not yet clearly.In order to study the exactly mechanism of CtIP,we carried out a series of related experiments.The experiment shows that it has no influence on cell cycle in U2 OS cell which interfere the CtIP,but,bring down the speed of survival and multiplication in damaged cell.CtIP can recruit to the DSBs damage site that chemical drug ETO,restriction enzymeAsiSI and UV-405 induced,and can co-localization with the marker of DSBs.It is found in the experiment extraction of chromatin and immunofluorescence,in the process of DSBs repair the ETO induced,the recruitment of CtIP reached the maximum when damage repair 1h.We also found that CtIP participate in the retardantregulate of cell cycle G2 which ETOinduced.The normal U2 OS cell can arrestat G2 after deal with ETO 21 h,the cell can pass the G2 in the cell which interfere the CtIP.In addition,we verification the formality of CtIP that recruit to the DSBs site is dimerization.It has recently reported that the expression quantity of CtIP has relevance to the breast cancer.Our experiment results shows that the expression quantity of CtIP is relatively high in the normal breast cancer cellMCF10 A,relative low in the low grade malignancy cell MCF7 and lowest in the high grade malignancy cell MDA-MB-231.KM plotter data anlysis indicates CtIP has significant correlation to disease-free survival(DFS),distant metastases-free survival(DMFS),overall survival(OS),post-progression survival(PPS)in breast cancer patients.The paper preliminarily discuss the mechanism of molecule CtIP during the process of DSBs repair and the relevance with breast cancer.It has laid the foundation for further study the role and mechanism of CtIP.