脱氧核糖鸟苷酸对染色质松弛程度的调控作用  

Regulation of chromatin condensation by dGTP

作　　者：李英杰 王小军[2] 刘聪[2] 曾鸣[2] 郭莲娣 LI Ying-jie;WANG Xiao-jun;LIU Cong;ZENG Ming;GUO Lian-di(School of Pharmacy,Southwest Minzu University,Chengdu 610041,China;West China Second University Hospital,Sichuan University,Chengdu 610041,China)

机构地区：[1]西南民族大学药学院,四川成都610041 [2]四川大学华西第二医院,四川成都610041

出　　处：《西南民族大学学报（自然科学版）》2024年第3期299-304,共6页Journal of Southwest Minzu University(Natural Science Edition)

基　　金：国家自然科学基金(81702795);四川省科技厅重大专项(2017FZ0034);中央高校基本科研业务费专项资金(2023KYZZ05N,2018NZD17);优秀学生培养工程项目(ZYN2024150)。

摘　　要：真核生物的染色质结构在基因转录、DNA修复等生物学过程中发生动态变化,其松弛程度和组蛋白修饰受到多种机制的严密调控.在研究DNA修复机制的过程中,发现敲除S期抑制基因(Spd1)可以逆转多种DNA损伤应答(DDR)突变体的表型缺陷,该遗传相互作用涉及到DDR的多个信号转导通路.Spd1的主要功能是抑制脱氧核糖核苷酸(dNTP)的生物合成,这说明敲除Spd1可以通过改变dNTP库的水平或组分来影响DNA损伤应答.进一步分析发现,Spd1缺陷促进染色质松弛,导致突变菌株的染色质对微球菌核酸酶的敏感,由此说明dNTP水平的增高可以促进染色质的紧密程度.最后,通过利用可以转运外源dNTP的FY2317菌株,制备原生质体,利用半离体的体系证明过量的dNTP,特别是脱氧核糖鸟苷酸(dGTP)可以模拟Spd1缺失菌株的表型,显著提高染色质的松弛程度.综上所述,研究发现了一种新的调控染色质松弛程度的遗传机制,可以影响DNA损伤修复的应答.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 Spd1was 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.

关 键 词：脱氧核糖核苷酸(dNTP) 脱氧核糖鸟苷酸(dGTP) 染色质浓缩 DNA复制 

分 类 号：S813[农业科学—畜牧学]