Feng Wenyi
Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA.
Genes (Basel). 2016 Dec 28;8(1):10. doi: 10.3390/genes8010010.
Eukaryotic cells are equipped with surveillance mechanisms called checkpoints to ensure proper execution of cell cycle events. Among these are the checkpoints that detect DNA damage or replication perturbations and coordinate cellular activities to maintain genome stability. At the forefront of damage sensing is an evolutionarily conserved molecule, known respectively in budding yeast and humans as Mec1 (Mitosis entry checkpoint 1) and ATR (Ataxia telangiectasia and Rad3-related protein). Through phosphorylation, Mec1/ATR activates downstream components of a signaling cascade to maintain nucleotide pool balance, protect replication fork integrity, regulate activation of origins of replication, coordinate DNA repair, and implement cell cycle delay. This list of functions continues to expand as studies have revealed that Mec1/ATR modularly interacts with various protein molecules in response to different cellular cues. Among these newly assigned functions is the regulation of RNA metabolism during checkpoint activation and the coordination of replication-transcription conflicts. In this review, I will highlight some of these new functions of Mec1/ATR with a focus on the yeast model organism.
真核细胞配备有称为检查点的监测机制，以确保细胞周期事件的正确执行。其中包括检测DNA损伤或复制扰动并协调细胞活动以维持基因组稳定性的检查点。在损伤感应的前沿是一种进化上保守的分子，在芽殖酵母和人类中分别称为Mec1（有丝分裂进入检查点1）和ATR（共济失调毛细血管扩张症和Rad3相关蛋白）。通过磷酸化，Mec1/ATR激活信号级联的下游成分，以维持核苷酸库平衡、保护复制叉完整性、调节复制起点的激活、协调DNA修复并实现细胞周期延迟。随着研究表明Mec1/ATR根据不同的细胞信号与各种蛋白质分子进行模块化相互作用，这些功能列表不断扩展。这些新赋予的功能包括在检查点激活期间对RNA代谢的调节以及复制-转录冲突的协调。在这篇综述中，我将重点介绍酵母模式生物，突出Mec1/ATR的一些新功能。
