| 项目编号 |
PRJCA035115 |
| 项目标题 |
PARylated AFF1 protein promotes transcriptional restart in response to DNA damage |
| 涉及领域 |
Medical |
| 数据类型 |
Epigenomics
Transcriptome or Gene expression
Raw sequence reads
|
| 物种名称 |
Homo sapiens
|
| 描述信息 |
As we all know, precise regulation of gene expression is vital for cell survival in response to diverse stresses, such as DNA damage. Although DNA damage triggers transcriptional repression through numerous pathways, the detailed mechanism driving transcriptional reactivation remains obscure. Given its central role in safeguarding genomic integrity during the cellular response to DNA damage, we speculate that Poly(ADP-ribose) polymerase 1 (PARP1) could be a key player in resolving this issue. In this study, we reported a novel function of PARP1 in transcriptional restart during DDR through a mechanism termed poly(ADP-ribose)-mediated stabilization (PARSTA) of AFF1. Upon DNA damage, PARP1 binds to and PARylates AFF1 in a region that is recognized by E3 ubiquitin ligase Siah1. This prevents Siah1-mediated ubiquitination of AFF1, thus reinforcing its protein stability and facilitating efficient restoration of transcriptional activity after DNA damage. In summary, our findings expand the role of PARP1 to include the transcriptional recovery phase in DDR and suggest that targeting the PARSTA pathway could be beneficial in diseases characterized by hyperactive PARP1 and elevated levels of AFF1 |
| 样品范围 |
Monoisolate |
| 发布日期 |
2025-07-30 |
| 出版信息 |
| PubMed ID |
文章标题 |
杂志名称 |
Doi |
发表年份 |
| 41062835
|
Stabilization of AFF1 by PARylation ensures transcriptional restart after DNA damage
|
Nature Chemical Biology
|
10.1038/s41589-025-02045-5
|
2025
|
|
|
| 项目资金来源 |
| 机构 |
项目类型 |
授权项目ID |
授权项目名称 |
| National Natural Science Foundation of China (NSFC)
|
|
32370591
|
|
| National Natural Science Foundation of China (NSFC)
|
|
32070632
|
|
| National Natural Science Foundation of China (NSFC)
|
|
92053114
|
|
| Ministry of Science and Technology of the People's Republic of China (MOST)
|
|
2020YFA0908100
|
|
| ZhejiangProvincial Natural Science Foundation of China
|
|
LR21C060002
|
|
|
|
| 提交者 |
song
hua
lu (huasong_lu@zju.edu.cn)
|
| 提交单位 |
Zhejiang University |
| 提交日期 |
2025-01-13 |
