Okazaki fragment maturation: DNA flap dynamics for cell proliferation and survival

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.

Automated summary

Unsuccessful processing of Okazaki fragments leads to DNA breaks accumulation, which is associated with various human diseases. The study focuses on the detection and repair of unprocessed Okazaki fragments and the consequences of improper Okazaki fragment maturation (OFM) on genome stability and cell viability, especially in cancer cells. The canonical OFM pathways and their regulation of genomic integrity and cell survival are examined, as well as the alternative error-prone OFM processes induced by environmental stresses, which may drive mutagenesis, cellular evolution, and resistance to cancer therapies.