Nucleases are a super family of enzymes that hydrolyze phosphodiester bonds present in genomes.They widely vary in substrates,causing differentiation in cleavage patterns and having a diversified role in maintaining g...Nucleases are a super family of enzymes that hydrolyze phosphodiester bonds present in genomes.They widely vary in substrates,causing differentiation in cleavage patterns and having a diversified role in maintaining genetic material.Through cellular evolution of prokaryotic to eukaryotic,nucleases become structure-specific in recognizing its own or foreign genomic DNA/RNA configurations as its substrates,including flaps,bubbles,and Holliday junctions.These special structural configurations are commonly found as intermediates in processes like DNA replication,repair,and recombination.The structure-specific nature and diversified functions make them essential to maintaining genome integrity and evolution in normal and cancer cells.In this article,we review their roles in various pathways,including Okazaki fragment maturation during DNA replication,end resection in homology-directed recombination repair of DNA double-strand breaks,DNA excision repair and apoptosis DNA fragmentation in response to exogenous DNA damage,and HIV life cycle.As the nucleases serve as key points for the DNA dynamics,cellular apoptosis,and cancer cell survival pathways,we discuss the efforts in the field in developing the therapeutic regimens,taking advantage of recently available knowledge of their diversified structures and functions.展开更多
基金This work was supported by National Institutes of Health(NIH)/National Cancer Institute(NCI)grants(R01CA073764,R01CA085344,and R01CA233664 to B.S.and R50CA211397 to L.Z.)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS,2023-I2M-3-006 to H.S.).
文摘Nucleases are a super family of enzymes that hydrolyze phosphodiester bonds present in genomes.They widely vary in substrates,causing differentiation in cleavage patterns and having a diversified role in maintaining genetic material.Through cellular evolution of prokaryotic to eukaryotic,nucleases become structure-specific in recognizing its own or foreign genomic DNA/RNA configurations as its substrates,including flaps,bubbles,and Holliday junctions.These special structural configurations are commonly found as intermediates in processes like DNA replication,repair,and recombination.The structure-specific nature and diversified functions make them essential to maintaining genome integrity and evolution in normal and cancer cells.In this article,we review their roles in various pathways,including Okazaki fragment maturation during DNA replication,end resection in homology-directed recombination repair of DNA double-strand breaks,DNA excision repair and apoptosis DNA fragmentation in response to exogenous DNA damage,and HIV life cycle.As the nucleases serve as key points for the DNA dynamics,cellular apoptosis,and cancer cell survival pathways,we discuss the efforts in the field in developing the therapeutic regimens,taking advantage of recently available knowledge of their diversified structures and functions.
