2019年11月15日 · Here, by using CRISPR-Cas9 engineered human cell lines, we identify a hitherto unknown, H2AX-independent, function of MDC1 mediated by its PST-repeat region. We show that the PST-repeat...

The DNA damage response (DDR) is comprised of a network of proteins that respond to DNA damage. Mediator of DNA Damage Checkpoint 1 (MDC1) plays an early and important role in the DDR. Recent data show that MDC1 binds multiple proteins that ...

We show that the PST-repeat region directly interacts with chromatin via the nucleosome acidic patch and mediates DNA damage-independent association of MDC1 with chromatin.

MDC1 protein is a regulator of the Intra-S phase and the G2/M cell cycle checkpoints and recruits repair proteins to the site of DNA damage. It is involved in determining cell survival fate in association with tumor suppressor protein p53. This protein also goes by the name Nuclear Factor with BRCT Domain 1 (NFBD1).

2019年11月15日 · Here, by using CRISPR-Cas9 engineered human cell lines, we identify a hitherto unknown, H2AX-independent, function of MDC1 mediated by its PST-repeat region. We show that the PST-repeat region directly interacts with chromatin via the nucleosome acidic patch and mediates DNA damage-independent association of MDC1 with chromatin.

组蛋白 H2AX 和 MDC1 是关键的 DNA 修复和 DNA 损伤信号蛋白。 当 DNA 双链断裂 (DSB) 发生时，H2AX 被磷酸化，然后招募 MDC1，MDC1 反过来又充当对接平台，促进其他因子（包括 53BP1）定位到 DSB 位点。 在这里，通过使用 CRISPR-Cas9 工程改造的人类细胞系，我们鉴定了 MDC1 由其 PST 重复区域介导的迄今为止未知的、不依赖于 H2AX 的功能。 我们发现 PST 重复区域通过核小体酸性补丁直接与染色质相互作用，并介导 MDC1 与染色质的 DNA 损伤无关 …

2025年1月10日 · Here we demonstrate that the PST repeat region of MDC1 is a mutlivalent nucleosome binding domain, sufficient to tether chromatin in multiple contexts. In mitotic cells the affinity of the PST repeats for chromatin is downregulated by phosphorylation to prevent chromosome missegregation, while still contributing to DNA break tethering by the ...

2009年12月29日 · Mediator of DNA Damage Checkpoint 1 (MDC1) plays an early and important role in the DDR. Recent data show that MDC1 binds multiple proteins that participate in various aspects of the DDR, positioning it at the core of the DDR. Furthermore, interactions with non-DDR proteins were also revealed, suggesting novel roles for MDC1.

MDC1 depletion promotes cisplatin induced cell death in cervical cancer cells. MDC1 plays a role in tumorigenesis of oral squamous cell carcinoma; The PST-repeat region directly interacts with chromatin via the nucleosome acidic patch and mediates DNA damage-independent association of MDC1 with chromatin.

2003年2月27日 · Here we identify a novel BRCA1 carboxy-terminal (BRCT) and forkhead-associated (FHA) domain-containing protein, MDC1 (mediator of DNA damage checkpoint protein 1), which works with H2AX to...