한빛사 논문
Hanyong Jin1,5, Boeun Lee1,5, Yongyang Luo2, Yuri Choi3, Eui-Hwan Choi1, Hong Jin2, Kee-Beom Kim1, Sang Beom Seo1, Yong-Hak Kim4, Hyung Ho Lee3,*, Keun Pil Kim1,*, Kangseok Lee1,* & Jeehyeon Bae2,*
1Department of Life Science, Chung-Ang University, Seoul 06974, Korea. 2School of Pharmacy, Chung-Ang University, Seoul 06974, Korea. 3Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 08826, Korea. 4Department of Microbiology, Catholic University of Daegu School of Medicine, Daegu 42472, Korea. 5These authors contributed equally: Hanyong Jin, Boeun Lee.
*Corresponding author
Abstract
The balance between major DNA double-strand break (DSB) repair pathways is influenced by binding of the Ku complex, a XRCC5/6 heterodimer, to DSB ends, initiating non-homologous end joining (NHEJ) but preventing additional DSB end resection and homologous recombination (HR). However, the key molecular cue for Ku recruitment to DSB sites is unknown. Here, we report that FOXL2, a forkhead family transcriptional factor, directs DSB repair pathway choice by acetylation-dependent binding to Ku. Upon DSB induction, SIRT1 translocates to the nucleus and deacetylates FOXL2 at lysine 124, leading to liberation of XRCC5 and XRCC6 from FOXL2 and formation of the Ku complex. FOXL2 ablation enhances Ku recruitment to DSB sites, imbalances DSB repair kinetics by accelerating NHEJ and inhibiting HR, and thus leads to catastrophic genomic events. Our study unveils the SIRT1-(de)acetylated FOXL2-Ku axis that governs the balance of DSB repair pathways to maintain genome integrity.
논문정보
관련 링크
연구자 키워드
관련분야 연구자보기
관련분야 논문보기
해당논문 저자보기