Parp1 deletion rescues cerebellar hypotrophy in xrcc1 mutant zebrafish
Semenova, S. A.; Nammi, D.; Garrett, G. A.; Margolin, G.; Sinclair, J. L.; Maroofian, R.; Caldecott, K. W.; Burgess, H. A.
Show 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.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Autism gene variants disrupt enteric neuron migration and cause gastrointestinal dysmotility 96%
- CMTr cap-adjacent 2`-O-ribose mRNA methyltransferases are required for reward learning and mRNA localization to synapses 96%
- Retinal input influences pace of neurogenesis but not cell-type configuration of the visual forebrain 95%
Similar papers in this journal
- Motor neurons are dispensable for the assembly of a sensorimotor circuit for gaze stabilization 96%
- Analysis of zebrafish periderm enhancers facilitates identification of a regulatory variant near human KRT8/18 95%
- Probe-Seq enables transcriptional profiling of specific cell types from heterogeneous tissue by RNA-based isolation 95%
Similar papers in this journal
- Dopey-dependent regulation of extracellular vesicles maintains neuronal morphology 95%
- Identifying determinants of synaptic specificity by integrating connectomes and transcriptomes 95%
- Evolutionary diversification reveals distinct somatic versus germline cytoskeletal functions of the Arp2 branched actin nucleator protein 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.