2023年10月13日 · RAP80 has been characterized as a component of the BRCA1-A complex and is responsible for the recruitment of BRCA1 to DNA double-strand breaks (DSBs). However, we and others found that the recruitment of RAP80 and BRCA1 were not absolutely temporally synchronized, indicating that other mechanisms, a …

2024年8月23日 · RAP80的UIM结构域能够特异性地识别并结合K63连接的多泛素链，以及泛素化的组蛋白H2A和H2B，这一过程进而诱导BRCA1-A复合物的招募。 然而，RAP80被招募到DNA损伤位点的具体机制目前尚不完全清楚。 DOT1L是一种组蛋白甲基转移酶，尽管它不包含SET结构域，但它能催化组蛋白H3第79位赖氨酸（H3K79）的一、二和三甲基化。 DOT1L...

2017年6月1日 · Receptor-associated protein 80 (RAP80) helps recruit BRCA1 to double-strand breaks (DSBs) through the scaffold protein CCDC98 (Abraxas) and facilitates DNA damage response (DDR). However, the...

BRCA1作为最早发现的乳腺癌抑制基因，它的突变可导致乳腺癌等相关肿瘤发生率明显升高，而RAP80是作为BRCA1发挥作用时的一个重要伴侣蛋白。 低BRCA1、低Rap80水平的患者，其中位生存期显著延长，这说明Rap80对肿瘤化疗效果可能起关键性的调节作用[14]。 2.4 RAP80磷酸化 大部分参与IR导致的DNA损伤的蛋白均被ATM磷酸化[15]。 RAP80也包含8个潜在的ATM磷酸化位点。 已有报到证实其中3个 (Ser101，Ser205，Ser402)在体外被 ATM 磷酸化[2，8，16]。 …

2007年5月25日 · We report the identification of receptor-associated protein 80 (RAP80) as a BRCA1-interacting protein in humans. RAP80 contains a tandem ubiquitin-interacting motif domain, which is required for its binding with ubiquitin in vitro and its damage-induced foci formation in vivo.

2022年2月1日 · In this study, we identify RAP80 as a key factor suppressing the vulnerability of ssDNA in R-loops during DSB repair, thereby preventing abnormalities in transcribed regions of the genome. We demonstrate that depletion of RAP80 results in accumulation of DNA-RNA hybrids and CtIP and a loss of ssDNA in R-loops.

2011年4月15日 · We propose a model in which the BRCA1-RAP80 complex limits nuclease accessibility to DSBs, thus preventing excessive end resection and potentially deleterious homology-directed DSB repair mechanisms that can impair genome integrity.

2011年4月15日 · RAP80 or BRCC36 deficiency resulted in elevated Mre11-CtIP-dependent 5' end resection with a concomitant increase in HDR mechanisms that rely on 3' single-stranded overhangs. We propose a model in which the BRCA1-RAP80 complex limits nuclease accessibility to DSBs, thus preventing excessive end resection and …

2024年8月22日，深圳大学医学部卡尔森国际肿瘤中心 朱卫国 教授团队在 PNAS 杂志上发表题为 DOT1L-mediated RAP80 methylation promotes BRCA1 recruitment to elicit DNA repair 的研究论文， 揭示了DOT1L介导RAP80的甲基化在BRCA1-A复合物招募到染色质以进行DNA损伤修复的关 …

2007年5月5日 · We report the interaction of the BRCA1 BRCT domain with RAP80, a ubiquitin-binding protein. RAP80 targets a complex containing the BRCA1-BARD1 (BRCA1-associated ring domain protein 1) E3 ligase and the deubiquitinating enzyme (DUB) BRCC36 to MDC1-γH2AX–dependent lysine 6 - and lysine 63-linked ubiquitin polymers at …