因此,细胞进化出了一个复杂的生化途径系统来处理这种威胁,统称为DNA损伤应答(DNA-damage response,简称DDR),以防止有害的突变被继续传递。 “合成致死”的概念用于描述两个功能性基因同时失活导致细胞死亡的现象,随着PARP抑制剂的成功,“合成致死”领域引起大家广泛的关注。在伴有DDR某条通路缺陷的肿瘤细胞中,DNA修复...
DNA damage response inhibitors in cancer therapy: lessons from the past, current status and future implicationsThe DNA damage response (DDR) is a network of proteins that coordinate DNA repair and cell-cycle checkpoints to prevent damage being transmitted to daughter cells. DDR defects lead to ...
DNA damage response inhibitors, for example BRCA1/2 germline mutated cells are sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. The aims of this review are to discuss specific DNA damage response defects in breast cancer and to present the current stage of development of various DDR...
Genome instability has been identified as one of the enabling hallmarks in cancer. DNA damage response (DDR) network is responsible for maintenance of genome integrity in cells. As cancer cells frequently carry DDR gene deficiencies or suffer from replicative stress, targeting DDR processes could indu...
The DNA damage response (DDR) is a signaling cascade that is triggered by DNA damage, involving the halting of cell cycle progression and repair. It is a key event leading to senescence, which is characterized by irreversible cell cycle arrest and the se
Poly(ADP-ribosylation) of proteins following DNA damage is well studied and the use of poly(ADP-ribose) polymerase (PARP) inhibitors as therapeutic agents is an exciting prospect for the treatment of many cancers. Poly(ADP-ribose) glycohydrolase (PARG) has endo- and exoglycosidase activities whi...
这表明,清除和降解失败的、潜在不稳定的修复中间产物(如CCF),可能是一种保护基因组完整性或抑制过度DNA损伤反应(DNA damage response, DDR)信号的机制。 表1 细胞质DNA的分子标记物 CCF 与疾病治疗 除了上述CCF和SASP的功能外,这些信号还可能对人类健康产生有害影响。在某些情况(如衰老)下,衰老细胞清除失败会导致...
由于临床进一步的需求,DNA损伤应答(DNA damage response,DDR)通路的基因组改变正成为不同瘤种的治疗新靶点[16-18]。铂类化合物和多聚ADP-核糖聚合酶抑制剂(poly ADP-ribose polymerase-inhibitors,PARPi)是目前具有抗DDR改变的肿瘤细胞活性的两大类药物,最初...
ZNF827 is a single-stranded DNA binding protein that regulates the ATR-CHK1 DNA damage response pathway Here, the authors characterise the zinc finger protein ZNF827 as a single stranded DNA binding protein that accumulates at stalled replication forks to activate the ATR-CHK1 pathway and engage...
Fig. 1: General overview of DNA damage response networks activate by DNA damage. Once cellular DNA damage occurs, the DDR is activated to protect damaged DNA integrity. The cell cycle is paused to provide cells an opportunity to activate DNA repair mechanisms. When the DNA damage is severe, ...