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

Xia，Wen1; Ci，Shusheng1; Li，Menghan1; Wang，Meina1; Dianov，Grigory L.1,2,3; Ma，Zhuang1; Li，Lulu1; Hua，Ke1; Alagamuthu，Karthick Kumar1; Qing，Lihong4; Luo，Libo4; Edick，Ashlin M.5; Liu，Lingjie6; Hu，Zhigang1; He，Lingfeng1; Pan，Feiyan1; Guo，Zhigang1

2019-11-01

10.1096/fj.201900308R

FASEB JOURNAL   影响因子和分区

0892-6638

1530-6860

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.

base excision repair DNA repair double-strand break

SCI

英语

其他

Russian Foundation for Basic Research (RFBR)[19-04-00067]

Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology

Biochemistry & Molecular Biology ; Biology ; Cell Biology

WOS:000507461600008

FEDERATION AMER SOC EXP BIOL

BIOLOGY & BIOCHEMISTRY

2-s2.0-85074377862

Scopus

1.Jiangsu Key Laboratory for Molecular and Medical BiotechnologyCollege of Life SciencesNanjing Normal University,Nanjing,China
2.Department of Natural SciencesNovosibirsk State University,Novosibirsk,Russian Federation
3.Department of OncologyOxford Institute for Radiation OncologyUniversity of Oxford,Oxford,United Kingdom
4.Seventh People's Hospital,Changzhou,China
5.,
6.College of Life ScienceSouthern University of Science and Technology,Shenzhen,China

Xia，Wen,Ci，Shusheng,Li，Menghan,et al. Two-way crosstalk between BER and c-NHEJ repair pathway is mediated by Pol-β and Ku70[J]. FASEB JOURNAL,2019,33(11):11668-11681.

Xia，Wen.,Ci，Shusheng.,Li，Menghan.,Wang，Meina.,Dianov，Grigory L..,...&Guo，Zhigang.(2019).Two-way crosstalk between BER and c-NHEJ repair pathway is mediated by Pol-β and Ku70.FASEB JOURNAL,33(11),11668-11681.

Xia，Wen,et al."Two-way crosstalk between BER and c-NHEJ repair pathway is mediated by Pol-β and Ku70".FASEB JOURNAL 33.11(2019):11668-11681.