Feline XLF accumulates at DNA damage sites in a Ku‐dependent manner
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 effec...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-06-01
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| Series: | FEBS Open Bio |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/2211-5463.12589 |
| _version_ | 1797989041103175680 |
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| author | Manabu Koike Yasutomo Yutoku Aki Koike |
| author_facet | Manabu Koike Yasutomo Yutoku Aki Koike |
| author_sort | Manabu Koike |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T08:13:56Z |
| format | Article |
| id | doaj.art-a215c8bcaf294b5d8553e3e630c18254 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-04-11T08:13:56Z |
| publishDate | 2019-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-a215c8bcaf294b5d8553e3e630c182542022-12-22T04:35:14ZengWileyFEBS Open Bio2211-54632019-06-01961052106210.1002/2211-5463.12589Feline XLF accumulates at DNA damage sites in a Ku‐dependent mannerManabu Koike0Yasutomo Yutoku1Aki Koike2National Institute of Radiological Sciences National Institutes for Quantum and Radiological Science and Technology Chiba JapanNational Institute of Radiological Sciences National Institutes for Quantum and Radiological Science and Technology Chiba JapanNational Institute of Radiological Sciences National Institutes for Quantum and Radiological Science and Technology Chiba JapanResistance 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.https://doi.org/10.1002/2211-5463.12589companion animalDNA double‐strand breakfelineKu80non‐homologous DNA‐end joiningcat |
| spellingShingle | Manabu Koike Yasutomo Yutoku Aki Koike Feline XLF accumulates at DNA damage sites in a Ku‐dependent manner FEBS Open Bio companion animal DNA double‐strand break feline Ku80 non‐homologous DNA‐end joining cat |
| title | Feline XLF accumulates at DNA damage sites in a Ku‐dependent manner |
| title_full | Feline XLF accumulates at DNA damage sites in a Ku‐dependent manner |
| title_fullStr | Feline XLF accumulates at DNA damage sites in a Ku‐dependent manner |
| title_full_unstemmed | Feline XLF accumulates at DNA damage sites in a Ku‐dependent manner |
| title_short | Feline XLF accumulates at DNA damage sites in a Ku‐dependent manner |
| title_sort | feline xlf accumulates at dna damage sites in a ku dependent manner |
| topic | companion animal DNA double‐strand break feline Ku80 non‐homologous DNA‐end joining cat |
| url | https://doi.org/10.1002/2211-5463.12589 |
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