Since the mediators of Alt-EJ are not well understood, I have sought to identify DNA damage response (DDR) factors important for this repair event. Using chromosomal break reporter assays, I surveyed an RNAi library targeting known DDR factors for siRNAs that cause a specific decrease in Alt-...
大多数DNA修复因子在衰老细胞中有所下调,导致修复活性降低,尤其是同源修复途径活性的降低。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...
Long-patch BER修复路径是通过DNA聚合酶的链置换合成(strand displacement synthesis)将损伤部位延续，然后...
1 1Department of Molecular Genetics and Microbiology, Center for Virology, Duke University Medical Center, 213 Research Dr., CARL 424, DUMC 3054, Durham, NC 27710, USA The DNA damage response (DDR) has emerged as a critical tumour suppressor pathway responding to cellular DNA replicative stress...
Mutations in DNA damage response (DDR) factors are associated with human infertility, which affects up to 15% of the population. The DDR is required during germ cell development and meiosis. One pathway implicated in human fertility is DNA translesion synthesis (TLS), which allows replication impe...
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...
Next, the XPB and XPD helicases, components of the multi-subunit transcription factor TFIIH, unwind the DNA duplex in the immediate vicinity of the lesion. The endonucleases XPG and ERCC1/XPF then cleave one strand of the DNA at positions 3' and 5' to the damage, respectively, generating ...
在这两种情况中,通过TLS,基因组的完整性和DNA复制的连贯性分别得以保持,但DNA损伤依然存在,需要在后续的修复过程中得到解决,因而TLS(以及HDGR)被认为是一种“损伤耐受机制(路径)”,简称DT机制(路径)-Damage Tolerance Mechanism(Pathway)。(15)(17)(18)(25-36)...
[9]Behrens A, van Deursen JM, Rudolph KL, et al. Impact of genomic damage and ageing on stem cell function[J]. Nat Cell Biol, 2014, 16(3): 201-207. DOI: 10.1038/ncb2928. [10]Blanpain C, Mohrin M, Sotiropoulou PA, et ...
TheDeinococcusprotease PprI senses DNA damage by directly interacting with single-stranded DNA Lu et al. show that single-stranded DNA produced as a result of DNA damage may directly activate PprI inDeinococcusspecies, triggering the DNA damage response. ...