| RRC ID |
87480
|
| 著者 |
Semenova SA, Nammi D, Garrett GB, Margolin G, Sinclair JL, Maroofian R, Caldecott KW, Burgess HA.
|
| タイトル |
Parp1 deletion rescues cerebellar hypotrophy in xrcc1 mutant zebrafish.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Defects in DNA single-strand break repair are associated with neurodevelopmental and neurodegenerative disorders. One such disorder is that resulting from mutations in XRCC1, a scaffold protein that plays a central role in DNA single-strand base repair. XRCC1 is recruited at sites of single-strand breaks by PARP1, a protein that detects and is activated by such breaks and is negatively regulated by XRCC1 to prevent excessive PARP binding and activity. Loss of XRCC1 leads to the toxic accumulation and activity of PARP1 at single-strand breaks leading to base excision repair defects, a mechanism that may underlie pathological changes in patients carrying deleterious XRCC1 mutations. Here, we demonstrate that xrcc1 knockdown impairs development of the cerebellar plate in zebrafish. In contrast, parp1 knockdown alone does not significantly affect neural development, and instead rescues the cerebellar defects observed in xrcc1 mutant larvae. These findings support the notion that PARP1 inhibition may be a viable therapeutic candidate in neurological disorders.
|
| 巻・号 |
15(1)
|
| ページ |
17043
|
| 公開日 |
2025-5-16
|
| DOI |
10.1038/s41598-025-01870-x
|
| PII |
10.1038/s41598-025-01870-x
|
| PMID |
40379758
|
| PMC |
PMC12084314
|
| MeSH |
Animals
Cerebellum* / abnormalities
Cerebellum* / metabolism
Cerebellum* / pathology
DNA Breaks, Single-Stranded
DNA Repair
Gene Deletion*
Gene Knockdown Techniques
Mutation
Poly (ADP-Ribose) Polymerase-1* / genetics
Poly (ADP-Ribose) Polymerase-1* / metabolism
X-ray Repair Cross Complementing Protein 1* / genetics
X-ray Repair Cross Complementing Protein 1* / metabolism
Zebrafish* / genetics
Zebrafish Proteins* / genetics
Zebrafish Proteins* / metabolism
|
| リソース情報 |
| ゼブラフィッシュ |
Tg(vglut2a:loxP-DsRed-loxP-GFP)
Tg(gad1b:|R|-GFP) |
