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Two‐way crosstalk between BER and c‐NHEJ repair pathway is mediated by Pol‐β and Ku70
Author(s) -
Xia Wen,
Ci Shusheng,
Li Menghan,
Wang Meina,
Dianov Grigory L.,
Ma Zhuang,
Li Lulu,
Hua Ke,
Alagamuthu Karthick Kumar,
Qing Lihong,
Luo Libo,
Edick Ashlin M.,
Liu Lingjie,
Hu Zhigang,
He Lingfeng,
Pan Feiyan,
Guo Zhigang
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201900308r
Subject(s) - ku70 , ku80 , dna repair , base excision repair , dna polymerase , crosstalk , dna damage , microbiology and biotechnology , biology , dna , methyl methanesulfonate , dna repair protein xrcc4 , chemistry , genetics , dna mismatch repair , physics , dna binding protein , gene , transcription factor , optics
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