DNA is highly vulnerable to spontaneous and environmental timely damage in living cells.DNA damage may cause genetic instability and increase cancer risk if the damages are not repaired timely and efficiently.Human ce...DNA is highly vulnerable to spontaneous and environmental timely damage in living cells.DNA damage may cause genetic instability and increase cancer risk if the damages are not repaired timely and efficiently.Human cells possess several DNA damage response(DDR)mechanisms to protect the integrity of their genome.Clarification of the mechanisms under-lying the DNA damage response following lethal damage will facilitate the identification of therapeutic targets for cancers.Histone post-translational modifications(PTMs)have been indicated to play different roles in the repair of DNA damage.In this context,histone PTMs regulate recruitment of downstream effectors,and facilitate appropriate repair response.This review outlines the current understanding of different histone PTMs in response to DNA dam-age repair,besides,enumerates the role of new type PTMs such as histone succinylation and crotonylation in regulating DNA damage repair processes.展开更多
Clipping of the histone H3 N-terminal tail has been implicated in multiple fundamental biological processes for a growing list of eukaryotes.H3 clipping,serving as an irreversible process to permanently remove some po...Clipping of the histone H3 N-terminal tail has been implicated in multiple fundamental biological processes for a growing list of eukaryotes.H3 clipping,serving as an irreversible process to permanently remove some post-translational modifications(PTMs),may lead to noticeable changes in chromatin dynamics or gene expression.The eukaryotic model organism Tetrahymena thermophila is among the first few eukaryotes that exhibits H3 clipping activity,wherein the first six amino acids of H3 are cleaved off during vegetative growth.Clipping only occurs in the transcriptionally silent micronucleus of the binucleated T.thermophila,thus offering a unique opportunity to reveal the role of H3 clipping in epigenetic regulation.However,the physiological functions of the truncated H3 and its protease(s)for clipping remain elusive.Here,we review the major findings of H3 clipping in T.thermophila and highlight its association with histone modifications and cell cycle regulation.We also summarize the functions and mechanisms of H3 clipping in other eukaryotes,focusing on the high diversity in terms of protease families and cleavage sites.Finally,we predict several protease candidates in T.thermophila and provide insights for future studies.展开更多
自噬是一种广泛存在于真核细胞中的溶酶体依赖性分解代谢途径,涉及细胞分化、饥饿耐受和免疫防御等生物学功能。其中,异体自噬被定义为真核细胞特异性识别并清除胞内病原微生物的过程,是免疫细胞行使宿主防御的重要方式。然而,许多病原...自噬是一种广泛存在于真核细胞中的溶酶体依赖性分解代谢途径,涉及细胞分化、饥饿耐受和免疫防御等生物学功能。其中,异体自噬被定义为真核细胞特异性识别并清除胞内病原微生物的过程,是免疫细胞行使宿主防御的重要方式。然而,许多病原微生物已经“开发”了特殊的毒力因子(包括效应蛋白质和表面蛋白质等),衍生出多种逃避或劫持自噬作用的策略。研究表明,调控自噬的信号复杂,涉及到多种自噬相关蛋白质(autophagy related proteins,ATG proteins)的精细调控。现已证实,自噬的关键步骤经历了广泛的蛋白质翻译后修饰(post-translational modifications,PTMs),例如磷酸化/去磷酸化、泛素化/去泛素化等。这些修饰作用通过影响蛋白质的结构、稳定性、活性及其在细胞中的定位,赋予了宿主细胞自噬调控高度的动态性和可逆性。此外,研究发现,病原微生物的毒力因子能够劫持宿主细胞中ATG蛋白的蛋白质翻译后修饰,干扰自噬的信号传递,从而对抗异体自噬并促进其在宿主细胞中的存活。本文总结了常见的蛋白质翻译后修饰在异体自噬中的作用,并重点关注病原微生物利用宿主蛋白质翻译后修饰操纵异体自噬,进而促进自身存活的相关机制,为探索异体自噬干预策略和控制病原微生物感染提供参考。展开更多
基金supported by National Natural Science Foundation of China(No.82071695,82060535)Natural Science Foundation of Gansu Province,China(No.21JR7RA450)。
文摘DNA is highly vulnerable to spontaneous and environmental timely damage in living cells.DNA damage may cause genetic instability and increase cancer risk if the damages are not repaired timely and efficiently.Human cells possess several DNA damage response(DDR)mechanisms to protect the integrity of their genome.Clarification of the mechanisms under-lying the DNA damage response following lethal damage will facilitate the identification of therapeutic targets for cancers.Histone post-translational modifications(PTMs)have been indicated to play different roles in the repair of DNA damage.In this context,histone PTMs regulate recruitment of downstream effectors,and facilitate appropriate repair response.This review outlines the current understanding of different histone PTMs in response to DNA dam-age repair,besides,enumerates the role of new type PTMs such as histone succinylation and crotonylation in regulating DNA damage repair processes.
基金supported by the National Natural Science Foundation of China(32125006,32070437)China National Postdoctoral Program for Innovative Talents(BX2021277)+2 种基金China Postdoctoral Science Foundation(2021M690144)Natural Science Foundation of Shandong Province of China(ZR2021QC046)Postdoctoral Applied Research Project of Qingdao.
文摘Clipping of the histone H3 N-terminal tail has been implicated in multiple fundamental biological processes for a growing list of eukaryotes.H3 clipping,serving as an irreversible process to permanently remove some post-translational modifications(PTMs),may lead to noticeable changes in chromatin dynamics or gene expression.The eukaryotic model organism Tetrahymena thermophila is among the first few eukaryotes that exhibits H3 clipping activity,wherein the first six amino acids of H3 are cleaved off during vegetative growth.Clipping only occurs in the transcriptionally silent micronucleus of the binucleated T.thermophila,thus offering a unique opportunity to reveal the role of H3 clipping in epigenetic regulation.However,the physiological functions of the truncated H3 and its protease(s)for clipping remain elusive.Here,we review the major findings of H3 clipping in T.thermophila and highlight its association with histone modifications and cell cycle regulation.We also summarize the functions and mechanisms of H3 clipping in other eukaryotes,focusing on the high diversity in terms of protease families and cleavage sites.Finally,we predict several protease candidates in T.thermophila and provide insights for future studies.
文摘自噬是一种广泛存在于真核细胞中的溶酶体依赖性分解代谢途径,涉及细胞分化、饥饿耐受和免疫防御等生物学功能。其中,异体自噬被定义为真核细胞特异性识别并清除胞内病原微生物的过程,是免疫细胞行使宿主防御的重要方式。然而,许多病原微生物已经“开发”了特殊的毒力因子(包括效应蛋白质和表面蛋白质等),衍生出多种逃避或劫持自噬作用的策略。研究表明,调控自噬的信号复杂,涉及到多种自噬相关蛋白质(autophagy related proteins,ATG proteins)的精细调控。现已证实,自噬的关键步骤经历了广泛的蛋白质翻译后修饰(post-translational modifications,PTMs),例如磷酸化/去磷酸化、泛素化/去泛素化等。这些修饰作用通过影响蛋白质的结构、稳定性、活性及其在细胞中的定位,赋予了宿主细胞自噬调控高度的动态性和可逆性。此外,研究发现,病原微生物的毒力因子能够劫持宿主细胞中ATG蛋白的蛋白质翻译后修饰,干扰自噬的信号传递,从而对抗异体自噬并促进其在宿主细胞中的存活。本文总结了常见的蛋白质翻译后修饰在异体自噬中的作用,并重点关注病原微生物利用宿主蛋白质翻译后修饰操纵异体自噬,进而促进自身存活的相关机制,为探索异体自噬干预策略和控制病原微生物感染提供参考。
