Department of Cancer Genetics and Epigenetics, Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
Department of Cancer Genetics and Epigenetics, Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
Trends Cell Biol. 2023 Mar;33(3):221-234. doi: 10.1016/j.tcb.2022.06.014. Epub 2022 Jul 22.
Unsuccessful processing of Okazaki fragments leads to the accumulation of DNA breaks which are associated with many human diseases including cancer and neurodegenerative disorders. Recently, Okazaki fragment maturation (OFM) has received renewed attention regarding how unprocessed Okazaki fragments are sensed and repaired, and how inappropriate OFM impacts on genome stability and cell viability, especially in cancer cells. We provide an overview of the highly efficient and faithful canonical OFM pathways and their regulation of genomic integrity and cell survival. We also discuss how cells induce alternative error-prone OFM processes to promote cell survival in response to environmental stresses. Such stress-induced OFM processes may be important mechanisms driving mutagenesis, cellular evolution, and resistance to radio/chemotherapy and targeted therapeutics in human cancers.
冈崎片段的加工失败会导致 DNA 断裂的积累，这与许多人类疾病有关，包括癌症和神经退行性疾病。最近，冈崎片段成熟（OFM）受到了新的关注，人们研究了未加工的冈崎片段是如何被感知和修复的，以及不适当的 OFM 如何影响基因组稳定性和细胞活力，特别是在癌细胞中。我们概述了高效且忠实的典型 OFM 途径及其对基因组完整性和细胞存活的调节。我们还讨论了细胞如何诱导易错的替代 OFM 过程，以促进细胞在应对环境压力时的存活。这种应激诱导的 OFM 过程可能是驱动人类癌症中突变、细胞进化以及对放疗/化疗和靶向治疗耐药的重要机制。
