Research output: Contribution to journal › Article › peer-review
Two-way crosstalk between BER and c-NHEJ repair pathway is mediated by Pol-β and Ku70. / Xia, Wen; Ci, Shusheng; Li, Menghan et al.
In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 33, No. 11, 01.11.2019, p. 11668-11681.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Two-way crosstalk between BER and c-NHEJ repair pathway is mediated by Pol-β and Ku70
AU - Xia, Wen
AU - Ci, Shusheng
AU - Li, Menghan
AU - Wang, Meina
AU - Dianov, Grigory L.
AU - Ma, Zhuang
AU - Li, Lulu
AU - Hua, Ke
AU - Alagamuthu, Karthick Kumar
AU - Qing, Lihong
AU - Luo, Libo
AU - Edick, Ashlin M.
AU - Liu, Lingjie
AU - Hu, Zhigang
AU - He, Lingfeng
AU - Pan, Feiyan
AU - Guo, Zhigang
N1 - Publisher Copyright: © FASEB
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
AB - 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.
KW - base excision repair
KW - DNA repair
KW - double-strand break
KW - DNA/metabolism
KW - DNA Damage/genetics
KW - Humans
KW - DNA Repair/genetics
KW - DNA Replication/genetics
KW - DNA Breaks, Double-Stranded
KW - DNA-Binding Proteins/metabolism
KW - DNA Polymerase beta/genetics
KW - Ku Autoantigen/metabolism
KW - COMPLEX
KW - PROTEIN
KW - STRAND BREAK REPAIR
KW - MECHANISM
KW - DNA-POLYMERASE-BETA
KW - DAMAGE
KW - MAINTENANCE
KW - BASE EXCISION-REPAIR
KW - END-JOINING PATHWAYS
KW - HOMOLOGOUS RECOMBINATION
UR - http://www.scopus.com/inward/record.url?scp=85074377862&partnerID=8YFLogxK
U2 - 10.1096/fj.201900308R
DO - 10.1096/fj.201900308R
M3 - Article
C2 - 31348687
AN - SCOPUS:85074377862
VL - 33
SP - 11668
EP - 11681
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 11
ER -
ID: 22090203