Genome Instability & Disease Volume 1. Issue 5 简介

文章来源: 作者: 发布时间:2020年09月18日 点击数: 字体:

 1. The impact of transcription-mediated replication stress on genome instability and human disease | Stefano Gnan, Yaqun Liu, Manuela Spagnuolo & Chun-Long Chen


Errors to DNA replication can result in genome instability and the subsequent development of serious diseases including cancer and neurological disorders. In this review, Chun-Long Chen and colleagues outline the main mechanisms by which transcription-mediated replication stress may affect DNA replication. These mechanisms include head-on transcription conflicts and transcription-dependent suppression of initiation across large genes. While it is clear that gene transcription has an essential role in shaping the landscape of human genome replication, high-throughput, single-cell approaches are now needed to delineate the complexities of the DNA replication program at the individual patient level.

DNA复制是一个受到严格调控的过程,细胞本身有一套机制确保在细胞周期中基因组得到精确的复制,一旦出错,将会导致复制错误甚至癌变等严重后果。基因转录是内源复制压力诱导基因组不稳定的主要来源,在这篇综述中,Chun-Long Chen团队介绍了转录介导的复制压力可能影响DNA复制,导致基因组不稳定和人类疾病的机制。这有助于我们进一步了解基因转录在DNA复制和各种相关疾病过程中的重要作用。

法国居里研究所和索邦大学的Chun-Long Chen教授为本文的通讯作者,Stefano Gnan为第一作者。




Chun-Long Chen教授 



2. Primary microcephaly with an unstable genome | Shibin Xu, Xingxuan Wu, Bin Peng, Sheng-Li Cao & Xingzhi Xu


Autosomal recessive primary microcephaly (MCPH) is a rare genetic disease of unknown origin. However, most of the known genes associated with this disorder are involved in maintaining genome stability. In this review, Xingzhi Xu and colleagues categorize these genes based on their known relationships with centrosome and spindle function, cell cycle regulation and chromosome dynamics. They also propose some novel functions of MCPH genes in terms of how they might interact with DNA replication and/or the DNA replication stress responses. Improving our understanding of the pathologic mechanisms underlying MCPH will no doubt help uncover the critical pathways involved in brain development and diseases governed by genome instability, including tumorigenesis.

MCPH (常染色体隐性原发性小头畸形)是一种起因未明的罕见遗传疾病,与MCPH相关的已知基因中,大多数具有维持基因组稳定性的功能。在这篇综述中,许兴智教授和他的同事对这些相关基因进行分类,提出了“MCPH基因在DNA复制和/或DNA复制应激反应以及肿瘤发生中的潜在新功能”的观点,为找到MCPH病因及治疗方案提供参考。







3. Deciphering p53 dynamics and cell fate in DNA damage response using mathematical modeling | Nanfei Yang, Tingzhe Sun & Pingping Shen


Great advances over the past 20 years have been made in understanding p53 function and its role as a tumor suppressor. However, our understanding of the complete p53 network in cancer remains incomplete. In this review, Pingping Shen and colleagues explain how mathematical models, including Boolean and Markov network approaches, are now being developed to study p53 dynamics. They explain that combining high-throughput measures of p53 activity with mathematical modeling will help us to delineate the complex mechanisms underlying the p53 network.

在过去20年中,人类在了解p53功能及其作为肿瘤抑制因子的作用方面已取得了重大进展。 但是,我们对癌症中完整的p53网络仍未能完全了解。 在本文中,沉萍萍及其同事讨论了如何开发数学模型来研究p53动力学。 他们提出,将p53活性的高通量检测与数学建模相结合将有助于我们了解p53网络背后的复杂机制。






4. The roles of TRAF3 mutation in the oncogenic progression and drug response of multiple myeloma | Sultan Abda Neja


Loss-of-function mutations to tumor necrosis factor receptor-associated factor 3 (TRAF3) commonly occur in patients with multiple myeloma (MM). The result is over-activation of the NF-kB pathway that ultimately enhances MM cell survival. In this review, Sultan Abda Neja outlines how TRAF3-driven NF-кB pathway activation leads to MM progression. He explains how deciphering this pathway has generated insight into drug responses in affected patients and opened avenues for therapeutic development.

肿瘤坏死因子受体相关因子3(TRAF3)突变是多发性骨髓瘤(MM)中最常见的抑癌突变之一。 在这篇综述中, Sultan Abda Neja介绍了TRAF3突变相关的NF-кB途径激活在MM致癌进展和药物反应中的作用,为我们对多发性骨髓瘤的治疗和机制的理解提供了参考。

作者为阿瓦萨大学的Sultan Abda Neja 助理教授



Sultan Abda Neja 助理教授



5. Lymphocyte cytosolic protein 1 (LCP1) is a novel TRAF3 dysregulation biomarker with potential prognostic value in multiple myeloma | Eun Myoung Shin, Sultan Abda Neja, Kerem Fidan, Joelle Yi Heng Chua, Tae-Hoon Chung, Nicolas Bertin, Vinay Tergaonkar, Wee-Joo Chng & Melissa Gaik-Ming Ooi


Data from a new study by Melissa Gaik-Ming Ooi and colleagues suggest that patients with multiple myeloma (MM) with a poor prognosis express high levels of LCP1. They consequently show that inhibiting LCP1 renders TRAF3-mutated MM cells sensitive to the proteasome inhibitor bortezomib. This finding implicates LCP1 as a novel NIK-driven marker of TRAF3-driven MM. Targeting LCP1 might constitute a novel therapeutic intervention for affected patients.

TNF受体相关因子3(TRAF3)功能障碍突变是多发性骨髓瘤(MM)中最常见的NF-κB途径突变。 Melissa Gaik-Ming Ooi及同事发现,在MM患者中,预后较差的患者LCP1表达较高,抑制LCP1可以使TRAF3突变的MM细胞对硼替佐米敏感,该项发现证明了LCP1是TRAF3功能障碍性MM中NIK驱动的生物标志物,为多发性骨髓瘤治疗提供新的思路。

本文的通讯作者为新加坡国立大学Yong Loo Lin医学院医学系的Melissa Gaik-Ming Ooi博士,新加坡分子细胞生物学研究所(IMCB)NFκB信号通路实验室的Eun Myoung Shin 和阿瓦萨大学的Sultan Abda Neja助理教授为并列第一作者。




Melissa Gaik-Ming Ooi博士




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