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Structure-specific nucleases in genome dynamics and strategies for targeting cancers

Journal of Molecular Cell Biology 2024年第5期16卷 3-18页

作者： Haitao Sun Megan Luo Mian Zhou Li Zheng Hongzhi Li R.Steven Esworthy Binghui Shen Medicinal Plant Resources and Protection Research Center Institute of Medicinal Plant DevelopmentChinese Academy of Medical SciencesPeking Union Medical CollegeBeĳing 100193China Department of Cancer Genetics and Epigenetics Beckman Research Institute of City of HopeDuarteCA 91010USA Department of Molecular and Cell Biology University of CaliforniaBerkeleyBerkeleyCA 94720USA

nucleases are a super family of enzymes that hydrolyze phosphodiester bonds present in *** widely vary in substrates,causing differentiation in cleavage patterns and having a diversified role in maintaining genetic *** 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 *** special structural configurations are commonly found as intermediates in processes like DNA replication,repair,and *** structure-specific nature and diversified functions make them essential to maintaining genome integrity and evolution in normal and cancer *** 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 *** 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.

关键词： structure-specific nucleases DNA replication nuclease inhibitors synthetic lethality

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