Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, USA
mBio. 2021 Mar 16;12(2):e03348-20. doi: 10.1128/mBio.03348-20.
Cell cycle checkpoints and DNA repair pathways contribute to maintaining genome integrity and are thought to be evolutionarily ancient and broadly conserved. For example, in the yeast and humans, DNA damage induces activation of a checkpoint effector kinase, Rad53p (human homolog Chk2), to promote cell cycle arrest and transcription of DNA repair genes. However, recent studies have revealed variation in the DNA damage response networks of some fungi. For example, Shor et al. (mBio 11:e03044-20, 2020, https://doi.org/10.1128/mBio.03044-20) demonstrate that in comparison to , the fungal pathogen has reduced activation of Rad53p in response to DNA damage. Consequently, some downstream targets that contribute to genome maintenance, such as DNA polymerases, are transcriptionally downregulated in Downregulation of genome maintenance genes likely contributes to higher rates of mitotic failure and cell death in This and other recent findings highlight evolutionary diversity in eukaryotic DNA damage responses.
细胞周期检查点和 DNA 修复途径有助于维持基因组完整性，被认为是古老而广泛保守的。例如，在酵母和人类中，DNA 损伤诱导检查点效应激酶 Rad53p（人同源物 Chk2）的激活，以促进细胞周期停滞和 DNA 修复基因的转录。然而，最近的研究揭示了一些真菌的 DNA 损伤反应网络的变化。例如，Shor 等人（mBio 11:e03044-20, 2020, https://doi.org/10.1128/mBio.03044-20）表明，与 相比，真菌病原体 对 DNA 损伤的 Rad53p 激活减少。因此，一些有助于 基因组维持的下游靶标，如 DNA 聚合酶，在 中转录下调。基因组维持基因的下调可能导致 有丝分裂失败和细胞死亡的更高比率。这一发现和其他最近的发现强调了真核生物 DNA 损伤反应的进化多样性。
