Rad9

Rad9

Rad9 蛋白質是一種 checkpoint 的調控蛋白質,其通過與 Rad1 和 Hus1 形成異三聚體,稱 9-1-1 複合物,在 checkpoint 中參與 DNA 損傷應答、DNA 修復等維持細胞周期的生物進程。

基本介紹

  • 外文名:Rad9
  • 基因全名:RAD9 homolog A (S. pombe)
  • 生物學功能:基因損傷修復
  • 本質:一種 checkpoint 的調控蛋白質
Rad9背景知識,Rad9A命名,Rad9的生物學功能,Rad9最新文獻,

Rad9背景知識

生物隨時隨地都面臨著內源或者外源的DNA損傷因子的攻擊。如一個正常的大鼠細胞的基因組DNA一天內可遭受約100,000次氧化損傷。為了防禦這些損傷因子引起的傷害,在長期的進化過程中,生物發展出了一套高度保守的DNA損傷修復系統來管理和修復各種DNA損傷,以維持基因組穩定性。細胞周期監控點就是其中一種重要的機制。當細胞中的DNA受到損傷時,細胞周期監控點暫時阻止或者減緩細胞周期的運行,待細胞中受損DNA得到修復後再恢復正常的細胞周期運轉。Rad9是一個進化上從酵母到人都高度保守的基因。已有的工作顯示,Rad9在G2/M和S/M監控點中發揮重要作用,並且參與DNA鹼基切除修復和同源重組修復。Rad9-MLH1間的相互作用可以被能引起DNA錯配的藥物MMS和MNU刺激增強。Rad9通過與MLH1的相互作用參與細胞的錯配修復。Rad9的甲基化誘導的S/M和G2/M細胞周期監控激活是通過Chk1磷酸化。Rad9在細胞中存在著甲基化的翻譯後修飾,此修飾對Rad9功能的發揮起著關鍵的作用。Rad9可以被PRMT5甲基化,並且甲基化位點為172,174和175位精氨酸。

Rad9A命名

基因全名:RAD9 homolog A (S. pombe)
蛋白全名:Cell cycle checkpoint control protein RAD9A
其它名稱:Cell cycle checkpoint control protein;DNA repair exonuclease rad9 homolog A;hRAD 9;hRAD9;Rad 9;RAD 9A;RAD9 homolog A;RAD9 homolog;Rad9a;RAD9A_HUMAN;

Rad9的生物學功能

  • Rad9與基因損傷修復
  • Rad9在細胞凋亡中的作用
  • Rad9與惡性腫瘤的研究進展

Rad9最新文獻

Checkpoint protein Rad9 plays an important role in nucleotide excision repair
Rad9, an evolutionarily conserved checkpoint gene with multiple functions for preserving genomic integrity, has been shown to play important roles in homologous recombination repair, base excision repair and mismatch repair. However, whether Rad9 has an impact on nucleotide excision repair remains unknown. Here we demonstrated that Rad9 was involved in nucleotide excision repair and loss of Rad9 led to defective removal of the UV-derived photoproduct 6-4PP (6,4 pyrimidine-pyrimidone) and the BPDE (anti-benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide)-DNA adducts in mammalian cells. We also demonstrated that Rad9 could co-localize with XPC in response to local UV irradiation. However, our data showed that Rad9 was not required for the photoproducts recognition step of nucleotide excision repair. Further investigation revealed that reduction of Rad9 reduced the UV-induced transcription of the genes of the nucleotide excision repair factors DDB2, XPC, DDB1 and XPB and DDB2 protein levels in human cells. Interestingly, knockdown of one subunit of DNA damage recognition complex, hHR23B impaired Rad9-loading onto UV-damaged chromatin. Based on these results, we suggest that Rad9 plays an important role in nucleotide excision repair through mechanisms including maintaining DDB2 protein level in human cells.
文中用到的抗體:
Rad9
Western blot detection of RAD9A in Hela,MCF7,3T3,COS7&Rat testis cell lysates using RAD9A antibody(1:500 diluted).Predicted band size:43KDa,Observed band size:55KDa
Rad9
Immunoprecipitation analysis of Hela & 3T3 cell lysates using RAD9A antibody.
RAD9 基因首先是在裂殖酵母突變體中被發現,是一個進化上高度保守的基因,RAD9 基因屬於 DNA 損傷反應系統(DNAdamage response)中的一個重要成員。該系統負責應對各種 DNA 損傷,起到維護基因組穩定的作用。很多研究表明,RAD9 基因參與細胞周期檢測點檢測、DNA 損傷修復和細胞凋亡,在維持基因組穩定性和抑制腫瘤細胞增殖方面起到重要作用。

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