The chromatin structure of eukaryotes undergoes dynamic changes during biological processes such as gene transcrip-tion and DNA repair,and its relaxation and histone modification are tightly regulated by multiple mechanisms.In the process of studying DNA repair mechanisms,it was found that knocking out the S-phase checkpoint gene(Spd1)could reverse the pheno-typic defects of various DNA damage response(DDR)mutants.This genetic interaction involved multiple signaling pathways of DDR.The main function of Spd1 was to inhibit the biosynthesis of deoxyribonucleotides(dNTP),indicating that knocking out Spd1 could affect the DNA damage response by altering the level or composition of the dNTP pool.Further analysis revealed that Spd1 defects promoted chromatin relaxation,making the chromatin of mutant strains sensitive to micrococcal nuclease,indicating that an increase in dNTP levels could promote chromatin compaction.Finally,by using the FY2317 strain that could transport exogenous dNTP,protoplasts were prepared,and it was demonstrated in a semi-in vitro system that an excess of dNTP,especially deoxyguanosine triphosphate(dGTP),could mimic the phenotype of Spd1-deficient strains,significantly increasing chromatin relaxation.In summary,this study discovered a new genetic mechanism for regulating chromatin relaxation,which could affect the response of DNA damage repair.
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