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| Status |
Public on Feb 01, 2022 |
| Title |
SPARCLE, a p53-induced lncRNA, controls apoptosis after genotoxic stress by promoting PARP-1 cleavage |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
p53, master transcriptional regulator of the genotoxic stress response, controls cell cycle arrest and apoptosis following DNA damage. Here we identify a p53-induced lncRNA SPARCLE (Suicidal PARP-1 Cleavage Enhancer) adjacent to miR-34b/c required for p53-mediated apoptosis. SPARCLE is a ~770 nucleotide, nuclear lncRNA induced one day after DNA damage. Despite low expression (<15 copies/cell), SPARCLE deletion increases DNA repair and reduces DNA damage-induced apoptosis as much as p53 deficiency, while its over-expression restores apoptosis in p53-deficient cells. SPARCLE does not alter gene expression. SPARCLE causes apoptosis by acting as a caspase-3 cofactor for PARP-1 cleavage, which separates its N-terminal (NT) DNA binding domain from PARP-1 catalytic domains. NT-PARP-1 binds to DNA breaks but, lacking its PARylation domains, does not initiate DNA repair. In fact, expressing NT-PARP-1 in SPARCLE-deficient cells increases unrepaired DNA damage and restores apoptosis after DNA damage. Thus, as a PARP-1 cleavage cofactor, SPARCLE enhances p53-induced apoptosis.
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| Overall design |
Strand-specific RNA-seq of HCT116 cells treated with doxorubicin (1 uM) or control media for 48h. Cells are WT, KO or Over-express SPARCLE. Two biological replicates per condition are sequenced
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| Contributor(s) |
Meza-Sosa KF, Lieberman J |
| Citation(s) |
35104452 |
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| Submission date |
Jan 29, 2020 |
| Last update date |
May 16, 2022 |
| Contact name |
Karla F Meza-Sosa |
| E-mail(s) |
[email protected]
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| Organization name |
UNAM
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| Department |
Institute for Biotechnology
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| Street address |
Av. Universidad
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| City |
Cuernavaca |
| State/province |
Morelos |
| ZIP/Postal code |
62210 |
| Country |
Mexico |
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| Platforms (1) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA603844 |
| SRA |
SRP245965 |
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