Dynamic changes in subcellular localization of cattle XLF during cell cycle,and focus formation of cattle XLF at DNA damage sites immediately afterirradiation

Journal of Veterinary Medical Science

Yasutomo YUTOKU²  Aki KOIKE²  Manabu KOIKE¹ 

[1] Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, 4�?9�?1 Anagawa, Inage-ku, Chiba 263�?8555, Japan;Radiation Risk Reduction Research, National Institute of Radiological Sciences, 4�?9�?1 Anagawa, Inage-ku, Chiba 263�?8555, Japan

关键词: cattle;    DNA damage;    domestic animal;    Ku70;    XLF;   

DOI  :  10.1292/jvms.14-0516

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(21)Clinically, many chemotherapeutics and ionizing radiation (IR) have beenapplied for the treatment of various types of human and animal malignancies. Thesetreatments kill tumor cells by causing DNA double-strand breaks (DSBs). Core factors ofclassical nonhomologous DNA-end joining (C-NHEJ) play a vital role in DSB repair. Thus, itis indispensable to clarify the mechanisms of C-NHEJ in order to develop next-generationchemotherapeutics for cancer. The XRCC4-like factor (XLF; also called Cernunnos or NHEJ1)is the lastly identified core NHEJ factor. The localization of core NHEJ factors mightplay a critical role in regulating NHEJ activity. The localization and function of XLFhave not been elucidated in animal species other than mice and humans. Domestic cattle(Bos taurus) are the most common and vital domestic animals in manycountries. Here, we show that the localization of cattle XLF changes dynamically duringthe cell cycle. Furthermore, EYFP-cattle XLF accumulates quickly at microirradiated sitesand colocalizes with the DSB marker γH2AX. Moreover, nuclear localization and accumulationof cattle XLF at DSB sites are dependent on 12 amino acids (288�?299) of the C-terminalregion of XLF (XLF CTR). Furthermore, basic amino acids on the XLF CTR are highlyconserved among domestic animals including cattle, goat and horses, suggesting that theCTR is essential for the function of XLF in domestic animals. These findings might beuseful to develop the molecular-targeting therapeutic drug taking XLF as a target moleculefor human and domestic animals.

【 授权许可】

Unknown