| RRC ID |
62815
|
| 著者 |
Jin H, Lee B, Luo Y, Choi Y, Choi EH, Jin H, Kim KB, Seo SB, Kim YH, Lee HH, Kim KP, Lee K, Bae J.
|
| タイトル |
FOXL2 directs DNA double-strand break repair pathways by differentially interacting with Ku.
|
| ジャーナル |
Nat Commun
|
| 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.
|
| 巻・号 |
11(1)
|
| ページ |
2010
|
| 公開日 |
2020-4-24
|
| DOI |
10.1038/s41467-020-15748-1
|
| PII |
10.1038/s41467-020-15748-1
|
| PMID |
32332759
|
| PMC |
PMC7181608
|
| MeSH |
Acetylation
Cell Line, Tumor
DNA Breaks, Double-Stranded*
DNA End-Joining Repair*
Forkhead Box Protein L2 / genetics
Forkhead Box Protein L2 / metabolism*
HEK293 Cells
Homologous Recombination
Humans
Ku Autoantigen / genetics
Ku Autoantigen / metabolism*
Mutation
Protein Binding / genetics
RNA, Small Interfering / metabolism
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Sirtuin 1 / metabolism
|
| IF |
12.121
|
| リソース情報 |
| ヒト・動物細胞 |
KGN(RCB1154) |
