RRC ID 59900
Author Koike M, Yutoku Y, Koike A.
Title Feline XLF accumulates at DNA damage sites in a Ku-dependent manner.
Journal FEBS Open Bio
Abstract Resistance to radiotherapy and chemotherapy is a common problem in the treatment of cancer in humans and companion animals, including cats. There is thus an urgent need to develop new treatments. Molecularly targeted therapies hold the promise of high specificity and significant cancer-killing effects. Accumulating evidence shows that DNA double-strand break (DSB) repair proteins, which function in Ku-dependent non-homologous DNA-end joining (NHEJ), are potential target molecules for next-generation cancer therapies. Although cancer radioresistance in cats has been previously described, there are no reports on feline Ku-dependent NHEJ. Here, we cloned and sequenced feline XLF cDNA and characterized X-ray repair cross-complementing protein 4-like factor (XLF), which is one of the core NHEJ proteins. We demonstrated that feline XLF localizes to the nuclei of feline cells and that feline XLF immediately accumulates at laser-induced DSB sites in a Ku-dependent manner. Amino acid sequence alignment analysis showed that feline XLF has only 80.9% identity with human XLF protein, while the predicted nuclear localization signal and putative 14-3-3-binding motif are perfectly conserved among human, cat, dog, chimpanzee, and mouse. These findings are consistent with the hypothesis that regulation of subcellular localization is important for the function of XLF. Furthermore, these findings may be useful in clarifying the mechanisms underlying feline Ku-dependent DSB repair and feline cell radioresistance, and possibly facilitate the development of new molecularly targeted therapies that target common proteins in human and feline cancers.
Volume 9(6)
Pages 1052-1062
Published 2019-6-1
DOI 10.1002/2211-5463.12589
PMID 31115163
PMC PMC6551493
MeSH Animals CHO Cells Cat Diseases / drug therapy Cats Cell Nucleus / metabolism Cricetulus DNA Breaks, Double-Stranded / radiation effects* DNA End-Joining Repair* DNA Repair Enzymes / genetics DNA Repair Enzymes / metabolism* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* HCT116 Cells Histones / metabolism Humans Ku Autoantigen / metabolism Molecular Targeted Therapy / veterinary Neoplasms / drug therapy Nuclear Localization Signals Pets / genetics Phosphorylation Sequence Alignment Transfection
IF 1.959
Times Cited 0
Human and Animal Cells HCT116(RCB2979), CHO-K1