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酵母 PCNA 卸载酶 Elg1 在引发 DNA 损伤检查点中的作用。

A role for the yeast PCNA unloader Elg1 in eliciting the DNA damage checkpoint.

机构信息

Amity Institute of Biotechnology, Amity University Kolkata, Kolkata, 700135, India.

School of Molecular Cell Biology and Biotechnology, Tel Aviv University, Ramat Aviv, 69978, Israel.

出版信息

Curr Genet. 2020 Feb;66(1):79-84. doi: 10.1007/s00294-019-01020-7. Epub 2019 Jul 22.

Abstract

During cell proliferation, the genome is constantly threatened by cellular and external factors. When the DNA is damaged, or when its faithful duplication is delayed by DNA polymerase stalling, the cells induce a coordinated response termed the DNA damage response (DDR) or checkpoint. Elg1 forms an RFC-like complex in charge of unloading the DNA polymerase processively factor PCNA during DNA replication and DNA repair. Using checkpoint-inducible strains, a recently published paper (Sau et al. in mBio 10(3):e01159-19. https://doi.org/10.1128/mbio.01159-19, 2019) uncovered a role for Elg1 in eliciting the DNA damage checkpoint (DC), one of the branches of the DDR. The apical kinase Mec1/ATR phosphorylates Elg1, as well as the adaptor proteins Rad9/53BP1 and Dpb11/TopBP1, which are recruited to the site of DNA damage to amplify the checkpoint signal. In the absence of Elg1, Rad9 and Dpb11 are recruited but fail to be phosphorylated and the signal is therefore not amplified. Thus, Elg1 appears to coordinate DNA repair and the induction of the DNA damage checkpoint.

摘要

在细胞增殖过程中,基因组不断受到细胞内外因素的威胁。当 DNA 受损,或者 DNA 聚合酶因停滞而延迟忠实复制时,细胞会引发一种称为 DNA 损伤反应(DDR)或检查点的协调反应。Elg1 在负责在 DNA 复制和 DNA 修复过程中卸载 DNA 聚合酶连续因子 PCNA 的 RFC 样复合物中形成。在使用检查点诱导菌株的情况下,最近发表的一篇论文(Sau 等人在 mBio 10(3):e01159-19. https://doi.org/10.1128/mBio.01159-19, 2019)揭示了 Elg1 在引发 DNA 损伤检查点(DC)中的作用,这是 DDR 的分支之一。顶端激酶 Mec1/ATR 磷酸化 Elg1 以及衔接蛋白 Rad9/53BP1 和 Dpb11/TopBP1,它们被招募到 DNA 损伤部位以放大检查点信号。在没有 Elg1 的情况下,Rad9 和 Dpb11 被招募但未能磷酸化,因此信号未被放大。因此,Elg1 似乎协调 DNA 修复和 DNA 损伤检查点的诱导。

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