Scholarlink

<p>The nucleotide excision repair (NER) mechanism is responsible for removing bulky DNA damage, such as pyrimidine dimers induced by ultraviolet (UV) light. The NER pathway excises the damaged strand through incisions at the 5’ and 3’ ends of the damage, with the 5’ incision catalyzed by the XPF-ERCC1 endonuclease complex. Here, we identify an XPF ortholog in <i>Trypanosoma brucei</i>, the causative agent of human African trypanosomiasis (sleeping sickness). XPF-deficient parasites exhibit hypersensitivity to UV irradiation and a slower rate of DNA damage repair. Consistent with its role in DNA repair, XPF localizes to the nucleus, associating with nucleoplasmic and nucleolar regions. Additionally, we demonstrate that TbXPF protects against intra- and inter-strand crosslinks induced by cisplatin and mitomycin C, respectively. The presence of a functional NER pathway in trypanosomes suggests that these organisms are susceptible to replication- and transcription-blocking DNA damage <i>in vivo</i>. Under genotoxic stress, genome stability and parasite survival may heavily rely on DNA repair systems such as NER which, for this reason, could be an effective target for chemotherapeutic interventions.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Role of the nucleotide excision repair endonuclease XPF in the kinetoplastid parasite Trypanosoma brucei

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月2日

查看全文
  • Claudia Gómez-Liñán,
  • María Sáez-Maldonado,
  • Laura Montosa-Hidalgo,
  • Luis Miguel Ruiz-Pérez,
  • Dolores González-Pacanowska,
  • Antonio E. Vidal

摘要

The nucleotide excision repair (NER) mechanism is responsible for removing bulky DNA damage, such as pyrimidine dimers induced by ultraviolet (UV) light. The NER pathway excises the damaged strand through incisions at the 5’ and 3’ ends of the damage, with the 5’ incision catalyzed by the XPF-ERCC1 endonuclease complex. Here, we identify an XPF ortholog in Trypanosoma brucei, the causative agent of human African trypanosomiasis (sleeping sickness). XPF-deficient parasites exhibit hypersensitivity to UV irradiation and a slower rate of DNA damage repair. Consistent with its role in DNA repair, XPF localizes to the nucleus, associating with nucleoplasmic and nucleolar regions. Additionally, we demonstrate that TbXPF protects against intra- and inter-strand crosslinks induced by cisplatin and mitomycin C, respectively. The presence of a functional NER pathway in trypanosomes suggests that these organisms are susceptible to replication- and transcription-blocking DNA damage in vivo. Under genotoxic stress, genome stability and parasite survival may heavily rely on DNA repair systems such as NER which, for this reason, could be an effective target for chemotherapeutic interventions.