Related Experiment Video For CP: Molecular biology
Updated: Aug 22, 2025

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy
Published on: June 8, 2018
NEIL3 contributes to the Fanconi anemia/BRCA pathway by promoting the downstream double-strand break repair step
Niu Li1, Yufei Xu2, Hongzhu Chen2
1Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Clinical Molecular Diagnostics for Pediatrics, Shanghai 200127, China.
Abstract:
Interstrand crosslinks (ICLs) repair by the canonical Fanconi anemia (FA) pathway generates double-strand breaks (DSBs), which are subsequently repaired by the homologous recombination (HR) pathway. Recent studies show that the NEIL3 DNA glycosylase repairs psoralen-ICLs by direct unhooking. However, whether and how NEIL3 regulates MMC and cisplatin-ICL repair remains unclear. Here we show that NEIL3 participates in DSB repair step of ICL repair by promoting HR pathway. Mechanistically, NEIL3 is recruited to the DSB sites through its GRF zinc finger motifs. NEIL3 interacts with the DSB resection machinery, including CtIP, the MRE11-RAD50-NBS1 (MRN) complex, and DNA2, which is mediated by the GRF zinc finger motifs. In addition, NEIL3 is necessary for the chromatin recruitment of the resection machinery, and depletion of NEIL3 decreases end resection and compromises HR. Taken together, our results show that NEIL3 plays an important role in MMC/cisplatin-ICL repair by promoting the HR step in FA/BRCA pathway.
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