Rescue from replication stress during mitosis.
Rescue from replication stress during mitosis.
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DOI：
10.1080/15384101.2017.1288322
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发表时间：
2017-04-03
期刊：
影响因子：
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通讯作者：
Naim V
中科院分区：
文献类型：
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作者：
Fragkos M;Naim V
基因组不稳定是癌症的标志，也是人类疾病的共同特征，其特征是生长缺陷、神经退化、癌症易感性和衰老。最近的证据表明，DNA复制应激是基因组不稳定和肿瘤发生的主要驱动因素。细胞在有丝分裂过程中可能存在复制不足或结构未解的DNA，在有丝分裂过程中有特定的途径来解决这些结构，这表明有丝分裂从复制应激中拯救(MRRs)是影响基因组稳定和细胞动态平衡的关键过程。癌基因激活或看守基因功能丧失后MRRs的解除调控可能是促进癌症发生和发展的染色体异常的原因。在这篇综述中，我们讨论了复制应激的原因和后果，重点讨论了它在有丝分裂中的持久性，以及它的解决机制和涉及的因素，以及不完全复制或异常的MRR在肿瘤发生、衰老和疾病中的潜在影响。
Genomic instability is a hallmark of cancer and a common feature of human disorders, characterized by growth defects, neurodegeneration, cancer predisposition, and aging. Recent evidence has shown that DNA replication stress is a major driver of genomic instability and tumorigenesis. Cells can undergo mitosis with under-replicated DNA or unresolved DNA structures, and specific pathways are dedicated to resolving these structures during mitosis, suggesting that mitotic rescue from replication stress (MRRS) is a key process influencing genome stability and cellular homeostasis. Deregulation of MRRS following oncogene activation or loss-of-function of caretaker genes may be the cause of chromosomal aberrations that promote cancer initiation and progression. In this review, we discuss the causes and consequences of replication stress, focusing on its persistence in mitosis as well as the mechanisms and factors involved in its resolution, and the potential impact of incomplete replication or aberrant MRRS on tumorigenesis, aging and disease.