Cloning, localization and focus formation at DNA damage sites of canineXRCC4

The Journal of Veterinary Medical Science

Yasutomo YUTOKU¹  Aki KOIKE¹  Manabu KOIKE¹ 

[1] National Institute of Radiological Sciences, NationalInstitutes for Quantum and Radiological Science and Technology, 4–9–1 Anagawa,Inage-ku, Chiba 263–8555, Japan

关键词: canine;    companion animal;    DNA damage;    Ku;    XRCC4;   

DOI  :  10.1292/jvms.16-0381

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

Various chemotherapies and radiation therapies are useful for killing cancercells mainly by inducing DNA double-strand breaks (DSBs). Uncovering the molecularmechanisms of DSB repair processes is crucial for developing next-generationradiotherapies and chemotherapeutics for human and animal cancers. XRCC4 plays a criticalrole in Ku-dependent nonhomologous DNA-end joining (NHEJ) in human cells, and is one ofthe core NHEJ factors. The localization of core NHEJ factors, such as human Ku70 and Ku80,might play a crucial role in regulating NHEJ activity. Recently, companion animals, suchas canines, have been proposed to be a good model in many aspects of cancer research.However, the localization and regulation mechanisms of core NHEJ factors in canine cellshave not been elucidated. Here, we show that the expression and subcellular localizationof canine XRCC4 changes dynamically during the cell cycle. Furthermore, EYFP-canine XRCC4accumulates quickly at laser-microirradiated DSB sites. The structure of a putative humanXRCC4 nuclear localization signal (NLS) is highly conserved in canine, chimpanzee andmouse XRCC4. However, the amino acid residue corresponding to the human XRCC4 K210,thought to be important for nuclear localization, is not conserved in canine XRCC4. Ourfindings might be useful for the study of the molecular mechanisms of Ku-dependent NHEJ incanine cells and the development of new radiosensitizers that target XRCC4.

【 授权许可】

Unknown