Metastasis suppressor NME1 promotes non-homologous end joining of DNA double-strand breaks

Renyu Xue; Yihan Peng; Baolin Han; Xiangpan Li; Yali Chen; Huadong Pei

doi:10.1016/j.dnarep.2019.03.003

Metastasis suppressor NME1 promotes non-homologous end joining of DNA double-strand breaks

DNA Repair (Amst). 2019 May:77:27-35. doi: 10.1016/j.dnarep.2019.03.003. Epub 2019 Mar 4.

Authors

Renyu Xue¹, Yihan Peng², Baolin Han³, Xiangpan Li⁴, Yali Chen⁵, Huadong Pei⁶

Affiliations

¹ State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Beijing Institute of Lifeomics, Beijing 102206, China.
² State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Beijing Institute of Lifeomics, Beijing 102206, China; Department of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Science, 2300 Eye Street, N.W., Washington, DC, 20037, USA; George Washington University Cancer Center, Washington, DC, 20052, USA.
³ Department of Radiotherapy, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Tianjin, 301800, China.
⁴ Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430062, China. Electronic address: rm001227@whu.edu.
⁵ State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Beijing Institute of Lifeomics, Beijing 102206, China. Electronic address: cyali_2000@163.com.
⁶ State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Beijing Institute of Lifeomics, Beijing 102206, China; Department of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Science, 2300 Eye Street, N.W., Washington, DC, 20037, USA; George Washington University Cancer Center, Washington, DC, 20052, USA; Cancer Center, Renmin Hospital of Wuhan University, Wuhan, 430062, China. Electronic address: huadongpei@gwu.edu.

PMID: 30875636
DOI: 10.1016/j.dnarep.2019.03.003

Abstract

NME1 (also known as NM23-H1) was the first identified tumor metastasis suppressor, which has been reported to link with genomic stability maintenance and cancer. However its underlying mechanisms are still not fully understood. Here we find that NME1 is required for non-homologous end joining (NHEJ) of DNA double-strand breaks (DSBs). Mechanistically, NME1 re-localizes to DNA damage sites in a Ku-XRCC4-dependent manner, and regulates downstream LIG4 recruitment and end joining efficiency. Furthermore, we show that the 3'-5' exonuclease activity of NME1 is critical for its function in NHEJ. Taken together, our findings identify NME1 as a novel NHEJ factor, and reveal how this metastasis suppressor promotes genome stability.

Keywords: 3′-5′ exonuclease; DNA double-strand breaks; Genomic stability; NHEJ; NME1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
DNA Breaks, Double-Stranded*
DNA End-Joining Repair*
DNA Ligase ATP / metabolism
DNA-Binding Proteins / metabolism
Humans
NM23 Nucleoside Diphosphate Kinases / metabolism*
Neoplasm Metastasis

Substances

DNA-Binding Proteins
LIG4 protein, human
NM23 Nucleoside Diphosphate Kinases
XRCC4 protein, human
DNA Ligase ATP