MRE11-RAD50-NBS1（MRN）复合物可以识别并结合DSB，然后募集并激活ATM。激活的ATM可以磷酸化CtIP（C-terminal-binding protein interacting protein），再与BRCA1（乳腺癌相关蛋白1）相互作用，形成BRCA1 / MRN / CtIP复合体，促进DNA末端切除，以形成单链DNA，从而促进 HR （同源重组 ...

2017年10月12日 · Here, we show that MDC1 interacts with a helix–loop–helix (HLH)-containing protein called inhibitor of DNA-binding 3 (ID3). In response to double-strand breaks (DSBs) in the genome, ATM...

2019年11月15日 · Histone H2AX and MDC1 are key DNA repair and DNA-damage signalling proteins. When DNA double-strand breaks (DSBs) occur, H2AX is phosphorylated and then recruits MDC1, which in turn serves as a...

2022年12月16日 · 在有丝分裂中，ATM依赖的H2AX磷酸化招募了DNA损伤检查点蛋白1（MDC1）的中介物，MDC1通过其酪蛋白激酶2（CK2）介导的磷酸化与TOPBP1和PP2A细胞抑制剂（CIP2A）结合。 TOPBP1和CIP2A形成丝状结构，将两个DSB末端连接在一起（未显示）。 DNA修复通路主要包括核苷酸切除修复、碱基切除修复、错配修复、同源重组以及非同源末端链接等。 在人类细胞中有两种主要的DSB修复途径，第一个是非同源端连接（NHEJ）途径，它修 …

The observed defects in meiosis, class switching, and DSB repair in MDC1 −/− mice suggest that MDC1 plays an important role in maintaining genomic stability. We used metaphase spreads of activated T cells to examine genomic stability of MDC1 +/+ and MDC1 −/− cells in the absence of exogenous DNA damaging agents.

2005年12月29日 · Here, we demonstrate that mammalian MDC1/NFBD1 directly binds to phospho-H2AX (γH2AX) by specifically interacting with the phosphoepitope at the γH2AX carboxyl terminus. Moreover, through a combination of biochemical, cell-biological, and X-ray crystallographic approaches, we reveal the molecular details …

DNA损伤修复相关基因 (mediator of DNA damage check point protein 1，MDC1)又称BRCT结构域1的核因子 (nuclear factor with BRCT domain protein 1，NFBD1)，是一种参与DNA损伤反应早期进程的支架蛋白，在调控DNA损伤应答和维持基因组稳定性方面发挥着重要功效。 本研究主要就MDC1的最新研究成果以及其在恶性肿瘤中的调控机制进行综述。 引用本文: 陈建胜, 王天楹, 王燕, 等. DNA损伤修复相关基因MDC1在恶性肿瘤发生发展中的调控作用 [J] . 国际遗传学杂志, …

2019年5月2日 · Here, we identify a highly conserved protein-interaction surface in MDC1 that is phosphorylated by CK2 and recognized by the DNA-damage response mediator protein TOPBP1. Disruption of MDC1-TOPBP1 binding causes a specific loss of TOPBP1 recruitment to DSBs in mitotic but not interphase cells, accompanied by mitotic radiosensitivity, increased ...

2024年9月20日 · To determine if diffusion of activated ATM could account for the observed behavior, we measured the exchange rate and diffusion constants of ATM and MDC1 within damaged and unperturbed chromatin. Using these measurements, we introduced a quantitative model in which the freely diffusing activated ATM phosphorylates H2AX.

2022年1月4日 · Pre-rRNA exists in the XY body, a DSB repair hub, during meiotic prophase, and colocalizes with DSB repair factors, such as MDC1, BRCA1 and TopBP1. Moreover, pre-rRNA-associated proteins and...