Maintaining chromosome and genome stability by the RPA-RNF20-SNF2H cascade.
Maintaining chromosome and genome stability by the RPA-RNF20-SNF2H cascade.
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DOI：
10.1073/pnas.2306455120
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发表时间：
2023-06-13
影响因子：
11.1
通讯作者：
Yan, Shan
中科院分区：
文献类型：
--
作者：
Driscoll, Garrett;Yan, Shan
细胞分裂对所有多细胞生物都是必不可少的，其有效性依赖于染色体分离和细胞蛋白的协调(1)。精确的染色体分离确保了染色体的稳定性，并防止了细胞分裂过程中的非整倍体(2)。此外，基因组DNA暴露于各种外部和内部的损伤来源，导致不同类型的DNA损伤，如双链断裂（dsb）（3,4）。为了应对DSBs，细胞进化出了几种DNA修复途径（如同源重组，HR）和DNA损伤反应（DDR）途径(如共济失调毛细血管扩张突变(ATM)/检查点激酶2 （Chk2）和ATM和rad3相关（ATR)/检查点激酶1 (Chk1)），以维持基因组的稳定性（3,4）。在这项PNAS研究中，Li等人研究了RING Finger Protein 20 （RNF20）与其他染色体/DNA代谢蛋白相互作用和协调的分子机制，以确保细胞中dsb的适当染色体分离和修复（图1A）(5)。先前的研究已经证明了染色体客运复合体（CPC）在调节微管-染色体附着以实现正确的染色体分离中的关键作用（6,7）。作为CPC的有丝分裂激酶成分，Aurora B被招募并定位于内着丝粒DNA和着丝粒。Aurora B自磷酸化其Thr232残基以激活其激酶功能，从而调节微管-染色体附着和染色体分离（7,8）。Aurora B的募集和磷酸化已被认为是染色体分离的重要调控机制(2)。Aurora B向着丝粒的募集是通过组蛋白翻译后修饰（PTMs）介导的，如磷酸化（例如，Haspin激酶磷酸化组蛋白H3， Bub1激酶磷酸化组蛋白H2A）；然而，目前尚不清楚极光B激酶自磷酸化是如何发生的（2,8）。组蛋白PTMs之间的相互作用和串扰，如泛素化、甲基化和磷酸化，在染色体分离和DNA修复以及染色体重组或重塑中起着不可或缺的关键作用(9)。赖氨酸120位点的组蛋白2B单泛素化（H2B-K120ub）主要由异二聚体RING Finger E3泛素连接酶RNF20/RNF40（酵母Bre1的同源物）和E2泛素偶联酶Rad6催化（9,10）。H2B-K120ub参与多种细胞过程，包括染色质重塑、转录调节、DDR、干细胞分化和组织发育（9-11）。H2B-K120ub的一个重要下游效应物是atp依赖的染色质重塑复合体SNF2H和RSF1，它们与含有H2B-K120的核小体相互作用，并参与染色质重塑和转录的调控（9,11）。多项研究表明RNF20/RNF40和H2B-K120ub在DSB修复中起重要作用（12-14）。此外,
Cell division is essential for all multicellular organisms, and its efficacy relies on chromosome segregation and the coordination of cellular proteins (1). Precise chromosome segregation ensures chromosomal stability and prevents aneuploidy during cell division (2). In addition, the genomic DNA is exposed to various external and internal sources of insults, leading to different types of DNA lesions such as double-strand breaks (DSBs)(3, 4). In response to DSBs, cells have evolved several DNA repair pathways (eg, homologous recombination, HR) and DNA damage response (DDR) pathways (eg, Ataxia-telangiectasia mutated (ATM)/Checkpoint kinase 2 (Chk2) and ATM-and Rad3-related (ATR)/Checkpoint kinase 1 (Chk1)) to maintain genome stability (3, 4). In this PNAS study, Li et al. investigated the molecular mechanisms by which the RING Finger Protein 20 (RNF20) interacts and coordinates with other chromosome/DNA metabolism proteins to ensure proper chromosome segregation and repair of DSBs in cells (Fig. 1A)(5). Previous studies have demonstrated the critical role of the chromosomal passenger complex (CPC) in regulating microtubule–chromosome attachment for proper chromosome segregation (6, 7). As the mitotic kinase component of the CPC, Aurora B is recruited to and localized in the inner centromere DNA and kinetochore. Aurora B autophosphorylates its Thr232 residue to activate its kinase function, thereby regulating microtubule–chromosome attachment and chromosome segregation (7, 8). The recruitment and phosphorylation of Aurora B has been recognized as essential regulatory mechanisms of chromosome segregation (2). The recruitment of Aurora B to the centromere is mediated by histone posttranslational modifications (PTMs) such as phosphorylation (eg, Histone H3 phosphorylation by Haspin kinase and H2A phosphorylation by Bub1 kinase); however, it is unclear how Aurora B kinase autophosphorylation occurs (2, 8). The interplay and cross talk between histone PTMs such as ubiquitination, methylation, and phosphorylation play an integral and crucial role in chromosome separation and DNA repair, as well as chromosome reorganization or remodeling (9). The Histone 2B mono-ubiquitination at Lysine 120 (H2B-K120ub) is primarily catalyzed by the heterodimeric RING Finger E3 ubiquitin ligase RNF20/RNF40 (the homolog of yeast Bre1) and the E2 ubiquitinconjugating enzyme Rad6 (9, 10). H2B-K120ub is implicated in various cellular processes, including chromatin remodeling, transcription regulation, DDR, stem cell differentiation, and tissue development (9–11). A crucial downstream effector of H2B-K120ub is the ATP-dependent chromatin remodeler complex SNF2H and RSF1, which interacts with nucleosomes containing H2B-K120 and contributes to the regulation of chromatin remodeling and transcription (9, 11). Several studies have shown the essential role RNF20/RNF40 and H2B-K120ub in DSB repair (12–14). Furthermore,
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影响因子：
6
作者：
通讯作者：
--
DOI：
10.1126/science.aan6490
发表时间：
2018-01-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kabeche L;Nguyen HD;Buisson R;Zou L
通讯作者：
Zou L
影响因子：
8
作者：
Yan, Shan;Sorrell, Melanie;Berman, Zachary
通讯作者：
Berman, Zachary
影响因子：
11.2
作者：
Chernikova SB;Razorenova OV;Higgins JP;Sishc BJ;Nicolau M;Dorth JA;Chernikova DA;Kwok S;Brooks JD;Bailey SM;Game JC;Brown JM
通讯作者：
Brown JM
影响因子：
16
作者：
Moyal L;Lerenthal Y;Gana-Weisz M;Mass G;So S;Wang SY;Eppink B;Chung YM;Shalev G;Shema E;Shkedy D;Smorodinsky NI;van Vliet N;Kuster B;Mann M;Ciechanover A;Dahm-Daphi J;Kanaar R;Hu MC;Chen DJ;Oren M;Shiloh Y
通讯作者：
Shiloh Y