S-phase checkpoint regulations that preserve replication and chromosome integrity upon dNTP depletion.
S-phase checkpoint regulations that preserve replication and chromosome integrity upon dNTP depletion.
复制标题
DOI：
10.1007/s00018-017-2474-4
复制
发表时间：
2017-07
期刊：
影响因子：
--
通讯作者：
Branzei D
中科院分区：
文献类型：
--
作者：
Giannattasio M;Branzei D
DNA复制应激是基因组不稳定性的一个重要来源，它产生于不同类型的DNA复制扰动，包括那些阻止复制叉进展的扰动。脱氧核苷酸三磷酸（dNTPs）的细胞池的抑制剂减慢整个基因组的DNA合成。在dNTP耗尽后，高度保守的复制检查点激酶途径，也称为S期检查点，保留了停滞的DNA复制叉的功能和结构，并防止染色体断裂。潜在的机制涉及复制叉的外在途径，例如涉及核糖核苷酸还原酶活性调节、起始点激发的时间程序和细胞周期转换的途径。此外，S期检查点调节复制体组分的功能以促进复制完整性。本文综述了复制检查点在dNTP缺失引起的复制应激中促进复制叉稳定性和基因组完整性的各种功能。
DNA replication stress, an important source of genomic instability, arises upon different types of DNA replication perturbations, including those that stall replication fork progression. Inhibitors of the cellular pool of deoxynucleotide triphosphates (dNTPs) slow down DNA synthesis throughout the genome. Following depletion of dNTPs, the highly conserved replication checkpoint kinase pathway, also known as the S-phase checkpoint, preserves the functionality and structure of stalled DNA replication forks and prevents chromosome fragmentation. The underlying mechanisms involve pathways extrinsic to replication forks, such as those involving regulation of the ribonucleotide reductase activity, the temporal program of origin firing, and cell cycle transitions. In addition, the S-phase checkpoint modulates the function of replisome components to promote replication integrity. This review summarizes the various functions of the replication checkpoint in promoting replication fork stability and genome integrity in the face of replication stress caused by dNTP depletion.