由于 PALB2 丧失 BRCA2/RAD51/RAD51C 结合功能导致的同源重组修复（HRR）缺陷
中文名称
通路描述
影响 PALB2 C 端 WD40 域（氨基酸 853-1186）的突变使其无法与 BRCA2、RAD51 和/或 RAD51C 相互作用。此外，WD40 域的破坏可导致 PALB2 核输出信号（NES）暴露及细胞质转位。影响 PALB2 C 端域的突变比影响 N 端域的突变更常见，已在家族性乳腺癌和 Fanconi 贫血中观察到，但体细胞突变也存在于散发性癌症中。表达 PALB2 突变体（缺陷于 BRCA2、RAD51 和/或 RAD51C 结合）的细胞在通过同源重组修复进行 DSBR 的能力降低，在 DSBR 位点形成较少的 RAD51 聚集体，并对 DNA 交联剂如米托霉素 C 敏感。
英文描述
Virion Assembly and Release This COVID-19 pathway has been created by a combination of computational inference from SARS-CoV-1 data (https://reactome.org/documentation/inferred-events) and manual curation, as described in the summation for the overall SARS-CoV-2 infection pathway.
The structures of complete SARS-CoV-2 virions, as well as their assembly stages, have been elucidated in great detail by cryo-electron microscopy methods. In particular, the Spike trimer is localized to ERGIC or Golgi compartments upon coexpression of E or M, which prevents syncytia formation (Boson et al, 2020). It is then transported via small transport vesicles to assembly sites (Klein et al, 2020; Mendonça et al, 2021; reviewed by Hardenbrook and Zhang, 2021). Based on work done in related coronaviruses, viral assembly is expected to occur at the ERGIC membrane (reviewed in Masters, 2006; Fehr and Perlman, 2015; Fung and Liu, 2019). Membrane protein components of the virus concentrate at the ERGIC membrane but are also found throughout the secretory system including at the plasma membrane. Accumulation at the site of viral assembly has been shown to depend on interaction between retrieval signals in the cytoplasmic tails of viral proteins and host factors such as the COPI coat, and likely involves repeated rounds of anterograde and retrograde traffic (McBride et al, 2007; Ujike et al, 2016; Tan et al, 2004; Tan et al, 2005; reviewed in McBride and Fielding, 2012; Chang et al, 2014).
Viral assembly is initiated by homotypic interactions of M protein (Tseng et al, 2010; Siu et al, 2008). This forms an M-lattice that contributes to the induction of membrane curvature and additionally acts as a scaffold for the recruitment of the other structural components of the virus (Voss et al, 2009). M protein makes interactions with each of the main components of the mature virus, including E, S and N (He et al, 2004; Luo et al, 2006; Siu et al, 2008; reviewed in Masters, 2006). Electron micrographic studies suggest the final size of the mature virus is ~100 nm. The ribonuclear particle is predominantly helical and is packaged with an outer diamter of ~ 16 nm (Neuman et al, 2006; Neuman et al, 2011; reviewed in Chang et al, 2014). These physical constraints suggest a final stoichiometry in the mature virion of 75 S trimers:1200 M proteins:300 N:1 RNA genome (Neuman et al, 2011; reviewed in Chang et al, 2014). Minor amounts of other viral proteins, including proteins E, 3a and 7a may also be components of the mature virus, although their functions are not well established (reviewed in Schoeman and Fielding, 2019; Liu et al, 2014).
The structures of complete SARS-CoV-2 virions, as well as their assembly stages, have been elucidated in great detail by cryo-electron microscopy methods. In particular, the Spike trimer is localized to ERGIC or Golgi compartments upon coexpression of E or M, which prevents syncytia formation (Boson et al, 2020). It is then transported via small transport vesicles to assembly sites (Klein et al, 2020; Mendonça et al, 2021; reviewed by Hardenbrook and Zhang, 2021). Based on work done in related coronaviruses, viral assembly is expected to occur at the ERGIC membrane (reviewed in Masters, 2006; Fehr and Perlman, 2015; Fung and Liu, 2019). Membrane protein components of the virus concentrate at the ERGIC membrane but are also found throughout the secretory system including at the plasma membrane. Accumulation at the site of viral assembly has been shown to depend on interaction between retrieval signals in the cytoplasmic tails of viral proteins and host factors such as the COPI coat, and likely involves repeated rounds of anterograde and retrograde traffic (McBride et al, 2007; Ujike et al, 2016; Tan et al, 2004; Tan et al, 2005; reviewed in McBride and Fielding, 2012; Chang et al, 2014).
Viral assembly is initiated by homotypic interactions of M protein (Tseng et al, 2010; Siu et al, 2008). This forms an M-lattice that contributes to the induction of membrane curvature and additionally acts as a scaffold for the recruitment of the other structural components of the virus (Voss et al, 2009). M protein makes interactions with each of the main components of the mature virus, including E, S and N (He et al, 2004; Luo et al, 2006; Siu et al, 2008; reviewed in Masters, 2006). Electron micrographic studies suggest the final size of the mature virus is ~100 nm. The ribonuclear particle is predominantly helical and is packaged with an outer diamter of ~ 16 nm (Neuman et al, 2006; Neuman et al, 2011; reviewed in Chang et al, 2014). These physical constraints suggest a final stoichiometry in the mature virion of 75 S trimers:1200 M proteins:300 N:1 RNA genome (Neuman et al, 2011; reviewed in Chang et al, 2014). Minor amounts of other viral proteins, including proteins E, 3a and 7a may also be components of the mature virus, although their functions are not well established (reviewed in Schoeman and Fielding, 2019; Liu et al, 2014).
所含基因
1 个基因