國家衛生研究院 NHRI:Item 3990099045/15742
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/15742


    Title: APLF facilitates interstrand DNA crosslink repair and replication fork protection to confer cisplatin resistance
    Authors: Wu, CK;Shiu, JL;Wu, CL;Hung, CF;Ho, YC;Chen, YT;Tung, SY;Yeh, CF;Shen, CH;Liaw, H;Su, WP
    Contributors: National Institute of Cancer Research
    Abstract: Replication stress converts the stalled forks into reversed forks, which is an important protection mechanism to prevent fork degradation and collapse into poisonous DNA double-strand breaks (DSBs). Paradoxically, the mechanism also acts in cancer cells to contribute to chemoresistance against various DNA-damaging agents. PARP1 binds to and is activated by stalled forks to facilitate fork reversal. Aprataxin and polynucleotide kinase/phosphatase-like factor (APLF) binds to PARP1 through the poly(ADP-ribose) zinc finger (PBZ) domain and is known to be involved in non-homologous end joining (NHEJ). Here, we identify a novel function of APLF involved in interstrand DNA crosslink (ICL) repair and fork protection. We demonstrate that PARP1 activity facilitates the APLF recruitment to stalled forks, enabling the FANCD2 recruitment to stalled forks. The depletion of APLF sensitizes cells to cisplatin, impairs ICL repair, reduces the FANCD2 recruitment to stalled forks, and results in nascent DNA degradation by MRE11 nucleases. Additionally, cisplatin-resistant cancer cells show high levels of APLF and homologous recombination-related gene expression. The depletion of APLF sensitizes cells to cisplatin and results in fork instability. Our results reveal the novel function of APLF to facilitate ICL repair and fork protection, thereby contributing to cisplatin-resistant phenotypes of cancer cells.
    Date: 2024-06-10
    Relation: Nucleic Acids Research. 2024 Jun 10;52(10):5676-5697.
    Link to: http://dx.doi.org/10.1093/nar/gkae211
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0305-1048&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001189391300001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85195708195
    Appears in Collections:[Che-Hung Shen] Periodical Articles

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