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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Tsai, Li-Kuang Peng, Min Chang, Chia-Chun Wen, Luan Liu, Lin Liang, Xiubin Chen, Y. Eugene Xu, Jie Sung, Li-Ying |
| Abstract | Background In eukaryotic cells, DNA double strand breaks (DSB) are primarily repaired by canonical non-homologous end joining (c-NHEJ), homologous recombination (HR) and alternative NHEJ (alt-NHEJ). Zinc finger and SCAN domain containing 4 (ZSCAN4), sporadically expressed in 1–5% mouse embryonic stem cells (mESCs), is known to regulate genome stability by promoting HR. Results Here we show that ZSCAN4 promotes DNA repair by acting with Poly (ADP-ribose) polymerase 1 (PARP1), which is a key member of the alt-NHEJ pathway. In the presence of PARP1, ZSCAN4-expressing mESCs are associated with lower extent of endogenous or chemical induced DSB comparing to ZSCAN4-negative ones. Reduced DSBs associated with ZSCAN4 are abolished by PARP1 inhibition, achieved either through small molecule inhibitor or gene knockout in mESCs. Furthermore, PARP1 binds directly to ZSCAN4, and the second ⍺-helix and the fourth zinc finger motif of ZSCAN4 are critical for this binding. Conclusions These data reveal that PARP1 and ZSCAN4 have a protein–protein interaction, and shed light on the molecular mechanisms by which ZSCAN4 reduces DSB in mESCs. |
| Related Links | https://cellandbioscience.biomedcentral.com/counter/pdf/10.1186/s13578-023-01140-1.pdf |
| Ending Page | 11 |
| Page Count | 11 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 20453701 |
| DOI | 10.1186/s13578-023-01140-1 |
| Journal | Cell & Bioscience |
| Issue Number | 1 |
| Volume Number | 13 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2023-10-24 |
| Access Restriction | Open |
| Subject Keyword | Cell Biology Microbiology Stem Cells Neurobiology Proteomics ZSCAN4 PARP1 DNA double strand breaks Mouse embryonic stem cells |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry, Genetics and Molecular Biology |
| Journal Impact Factor | 6.1/2023 |
| 5-Year Journal Impact Factor | 7/2023 |
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