Two-way crosstalk between BER and c-NHEJ repair pathway is mediated by Pol-β and Ku70

Wen Xia, Shusheng Ci, Menghan Li, Meina Wang, Grigory L. Dianov, Zhuang Ma, Lulu Li, Ke Hua, Karthick Kumar Alagamuthu, Lihong Qing, Libo Luo, Ashlin M. Edick, Lingjie Liu, Zhigang Hu, Lingfeng He, Feiyan Pan, Zhigang Guo

Результат исследования: Научные публикации в периодических изданияхстатья

Аннотация

Multiple DNA repair pathways may be involved in the removal of the same DNA lesion caused by endogenous or exogenous agents. Although distinct DNA repair machinery fulfill overlapping roles in the repair of DNA lesions, the mechanisms coordinating different pathways have not been investigated in detail. Here, we show that Ku70, a core protein of nonhomologous end-joining (NHEJ) repair pathway, can directly interact with DNA polymerase-β (Pol-β), a central player in the DNA base excision repair (BER), and this physical complex not only promotes the polymerase activity of Pol-β and BER efficiency but also enhances the classic NHEJ repair. Moreover, we find that DNA damages caused by methyl methanesulfonate (MMS) or etoposide promote the formation of Ku70-Pol-β complexes at the repair foci. Furthermore, suppression of endogenous Ku70 expression by small interfering RNA reduces BER efficiency and leads to higher sensitivity to MMS and accumulation of the DNA strand breaks. Similarly, Pol-β knockdown impairs total-NHEJ capacity but only has a slight influence on alternative NHEJ. These results suggest that Pol-β and Ku70 coordinate 2-way crosstalk between the BER and NHEJ pathways.—Xia, W., Ci, S., Li, M., Wang, M., Dianov, G. L., Ma, Z., Li, L., Hua, K., Alagamuthu, K. K., Qing, L., Luo, L., Edick, A. M., Liu, L., Hu, Z., He, L., Pan, F., Guo, Z. Two-way crosstalk between BER and c-NHEJ repair pathway is mediated by Pol-β and Ku70. FASEB J. 33, 11668-11681 (2019). www.fasebj.org.

Язык оригиналаанглийский
Страницы (с-по)11668-11681
Число страниц14
ЖурналFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Том33
Номер выпуска11
DOI
СостояниеОпубликовано - 1 ноя 2019

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    Xia, W., Ci, S., Li, M., Wang, M., Dianov, G. L., Ma, Z., Li, L., Hua, K., Alagamuthu, K. K., Qing, L., Luo, L., Edick, A. M., Liu, L., Hu, Z., He, L., Pan, F., & Guo, Z. (2019). Two-way crosstalk between BER and c-NHEJ repair pathway is mediated by Pol-β and Ku70. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33(11), 11668-11681. https://doi.org/10.1096/fj.201900308R