| RRC ID |
85396
|
| 著者 |
Ozaki K, Kato R, Yasuhara T, Uchihara Y, Hirakawa M, Abe Y, Shibata H, Kawabata-Iwakawa R, Shakayeva A, Kot P, Miyagawa K, Suzuki K, Matsuda N, Shibata A, Yamauchi M.
|
| タイトル |
Involvement of the splicing factor SART1 in the BRCA1-dependent homologous recombination repair of DNA double-strand breaks.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Although previous studies have reported that pre-mRNA splicing factors (SFs) are involved in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR), their exact role in promoting HR remains poorly understood. Here, we showed that SART1, an SF upregulated in several types of cancer, promotes DSB end resection, an essential first step of HR. The resection-promoting function of SART1 requires phosphorylation at threonine 430 and 695 by ATM/ATR. SART1 is recruited to DSB sites in a manner dependent on transcription and its RS domain. SART1 is epistatic with BRCA1, a major HR factor, in the promotion of resection, especially transcription-associated resection in the G2 phase. SART1 and BRCA1 accumulate at DSB sites in an interdependent manner, and epistatically counteract the resection blockade posed by 53BP1 and RIF1. Furthermore, chromosome analysis demonstrated that SART1 and BRCA1 epistatically suppressed genomic alterations caused by DSB misrepair in the G2 phase. Collectively, these results indicate that SART1 and BRCA1 cooperatively facilitate resection of DSBs arising in transcriptionally active genomic regions in the G2 phase, thereby promoting faithful repair by HR, and suppressing genome instability.
|
| 巻・号 |
14(1)
|
| ページ |
18455
|
| 公開日 |
2024-8-8
|
| DOI |
10.1038/s41598-024-68926-2
|
| PII |
10.1038/s41598-024-68926-2
|
| PMID |
39117746
|
| PMC |
PMC11310344
|
| MeSH |
Ataxia Telangiectasia Mutated Proteins / genetics
Ataxia Telangiectasia Mutated Proteins / metabolism
BRCA1 Protein* / genetics
BRCA1 Protein* / metabolism
Cell Line, Tumor
DNA Breaks, Double-Stranded*
Epistasis, Genetic
G2 Phase / genetics
Humans
Phosphorylation
Recombinational DNA Repair*
Serine-Arginine Splicing Factors / genetics
Serine-Arginine Splicing Factors / metabolism
Telomere-Binding Proteins / genetics
Telomere-Binding Proteins / metabolism
Tumor Suppressor p53-Binding Protein 1 / genetics
Tumor Suppressor p53-Binding Protein 1 / metabolism
|
| IF |
3.998
|
| リソース情報 |
| 遺伝子材料 |
pIRES-3xFLAG-SART1 WT (siRNA-resistant) (RDB20928)
pEGFP-C3-SART1 WT (RDB20929) |
