Zhang Hong, Taylor Jena, Siede Wolfram
Department of Radiation Oncology and the Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
J Biol Chem. 2003 Mar 14;278(11):9382-7. doi: 10.1074/jbc.M300061200. Epub 2003 Jan 8.
The recognition of DNA double-stranded breaks or single-stranded DNA gaps as a precondition for cell cycle checkpoint arrest has been well established. However, how bulky base damage such as UV-induced pyrimidine dimers elicits a checkpoint response has remained elusive. Nucleotide excision repair represents the main pathway for UV dimer removal that results in strand interruptions. However, we demonstrate here that Rad53p hyperphosphorylation, an early event of checkpoint signaling in Saccharomyces cerevisiae, is independent of nucleotide excision repair (NER), even if replication as a source of secondary DNA damage is excluded. Thus, our data hint at primary base damage or at UV damage (primary or secondary) that does not need to be processed by NER as the relevant substrate of damage-sensing checkpoint proteins.
DNA双链断裂或单链DNA缺口作为细胞周期检查点停滞的前提条件已得到充分证实。然而，诸如紫外线诱导的嘧啶二聚体等大量碱基损伤如何引发检查点反应仍不清楚。核苷酸切除修复是去除紫外线二聚体导致链中断的主要途径。然而，我们在此证明，Rad53p过度磷酸化是酿酒酵母检查点信号传导的早期事件，它独立于核苷酸切除修复（NER），即使排除作为二次DNA损伤来源的复制情况也是如此。因此，我们的数据表明，不需要通过NER处理的初级碱基损伤或紫外线损伤（初级或次级）是损伤感应检查点蛋白的相关底物。
