Screen To Identify DSB Response Proteins And Their Roles In Double-strand Break Repair Response

In eukaryotic cells,maintenance of genomic stability is the most important action in the whole lifespan.Cells are constantly under threat from the physical and chemical of DNA damageing agents.The most cytotoxic forms of DNA damage type is DNA double-strand break(DSB).Unrepaired DSB will cause genome intergrity,apoptosis,chromosomal rearrangements,oncogene activation or tumor suppressor genes inactivation.A series of proteins were activated and recruided to DSBR reagion.Recent research focuses on two types of repair,homologous recombination(HR)and non-homologous end joining(NHEJ).The choice between the two repair methods is related to the cell cycle and is closely regulated.In this paper,we use the method of immunoprecipitation combined with mass spectrometry to screen the new protein related to DSBR.We found the protein ZMYM4,which was involved in this pathway,and verified the function by immunofluorescence,class switch and telomere fusion.Further study on the upstream and downstream of ATM phosphorylation,53BP1 and RIF1.We found that the phosphorylation site of 53BP1 is necessary for ATM activation and RIF 1 recruited into the DSB complex,and phosphorylation of 53BP1 is upstream of ATM activation.For even 53BP1 simulated still can not recruit RIF1.This has an enlightening effect on subsequent research.