Identification of Nanog As a Novel Inhibitor of Rad51

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2022 Feb 27

PMID 35220392

Authors

Ying Xin

Juanjuan Wang

Yahong Wu

Qianqian Li

Mingyang Dong

Chang Liu

Qijia He

Ruifeng Wang

Dian Wang

Sen Jiang

Wei Xiao

Yang Tian

Weiwei Zhang

Affiliations

Soon will be listed here.

Abstract

To develop inhibitors targeting DNA damage repair pathways is important to improve the effectiveness of chemo- and radiotherapy for cancer patients. Rad51 mediates homologous recombination (HR) repair of DNA damages. It is widely overexpressed in human cancers and overwhelms chemo- and radiotherapy-generated DNA damages through enhancing HR repair signaling, preventing damage-caused cancer cell death. Therefore, to identify inhibitors of Rad51 is important to achieve effective treatment of cancers. Transcription factor Nanog is a core regulator of embryonic stem (ES) cells for its indispensable role in stemness maintenance. In this study, we identified Nanog as a novel inhibitor of Rad51. It interacts with Rad51 and inhibits Rad51-mediated HR repair of DNA damage through its C/CD2 domain. Moreover, Rad51 inhibition can be achieved by nanoscale material- or cell-penetrating peptide (CPP)-mediated direct delivery of Nanog-C/CD2 peptides into somatic cancer cells. Furthermore, we revealed that Nanog suppresses the binding of Rad51 to single-stranded DNAs to stall the HR repair signaling. This study provides explanation for the high γH2AX level in unperturbed ES cells and early embryos, and suggests Nanog-C/CD2 as a promising drug candidate applied to Rad51-related basic research and therapeutic application studies.

Citing Articles

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