Postreplication repair and PCNA modification in Schizosaccharomyces pombe

Postreplication repair and PCNA modification in Schizosaccharomyces pombe
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DOI:
10.1091/mbc.e05-11-1008
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发表时间:
2006-07-01
影响因子:
3.3
通讯作者:
Lehmann, Alan R.
Lehmann, Alan R.
中科院分区:
生物学3区
文献类型:
--
作者:
Frampton, Jonathan;Irmisch, Anja;Lehmann, Alan R.

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增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)的泛素化在真核生物DNA损伤后的复制调控中起着至关重要的作用,但其具体机制在不同的生物体中存在差异。我们研究了裂殖酵母中PCNA的修饰。我们发现,在响应紫外线照射,PCNA是单和多泛素化的方式类似于在酿酒酵母。而在未受损的裂殖酵母细胞中,PCNA在S期被泛素化,而在S期被泛素化。在酿酒酵母中,它被sumoylated。此外,我们发现,与S。在酿酒酵母中,PCNA泛素化缺陷的突变体也对电离辐射敏感,并且PCNA在细胞暴露于电离辐射后以类似于对UV照射的响应的方式被泛素化。我们发现,PCNA修饰和细胞周期检查点代表两个独立的信号,在DNA损伤。最后,我们意外地发现,当细胞被阻滞在G2期时,PCNA是泛素化的,以响应DNA损伤。
Ubiquitination of proliferating cell nuclear antigen (PCNA) plays a crucial role in regulating replication past DNA damage in eukaryotes, but the detailed mechanisms appear to vary in different organisms. We have examined the modification of PCNA in Schizosaccharomyces pombe. We find that, in response to UV irradiation, PCNA is mono- and poly-ubiquitinated in a manner similar to that in Saccharomyces cerevisiae. However in undamaged Schizosaccharomyces pombe cells, PCNA is ubiquitinated in S phase, whereas in S. cerevisiae it is sumoylated. Furthermore we find that, unlike in S. cerevisiae, mutants defective in ubiquitination of PCNA are also sensitive to ionizing radiation, and PCNA is ubiquitinated after exposure of cells to ionizing radiation, in a manner similar to the response to UV-irradiation. We show that PCNA modification and cell cycle checkpoints represent two independent signals in response to DNA damage. Finally, we unexpectedly find that PCNA is ubiquitinated in response to DNA damage when cells are arrested in G2.