Fragkos Michalis, Naim Valeria
a CNRS UMR8200 , University Paris-Saclay , Gustave Roussy, Villejuif , France.
Cell Cycle. 2017 Apr 3;16(7):613-633. doi: 10.1080/15384101.2017.1288322. Epub 2017 Feb 6.
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.
基因组不稳定是癌症的一个标志，也是人类疾病的一个共同特征，其特征包括生长缺陷、神经退行性变、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。细胞可能会带着未完全复制的DNA或未解决的DNA结构进行有丝分裂，并且特定的途径专门用于在有丝分裂期间解决这些结构，这表明从复制应激中进行有丝分裂拯救（MRRS）是影响基因组稳定性和细胞稳态的关键过程。癌基因激活或维持基因功能丧失后MRRS的失调可能是促进癌症起始和进展的染色体畸变的原因。在这篇综述中，我们讨论了复制应激的原因和后果，重点关注其在有丝分裂中的持续存在以及参与其解决的机制和因素，以及不完全复制或异常MRRS对肿瘤发生、衰老和疾病的潜在影响。
