Unknown

Dataset Information

0

Nuclear DJ-1 Regulates DNA Damage Repair via the Regulation of PARP1 Activity.


ABSTRACT: DNA damage and defective DNA repair are extensively linked to neurodegeneration in Parkinson's disease (PD), but the underlying molecular mechanisms remain poorly understood. Here, we determined that the PD-associated protein DJ-1 plays an essential role in modulating DNA double-strand break (DSB) repair. Specifically, DJ-1 is a DNA damage response (DDR) protein that can be recruited to DNA damage sites, where it promotes DSB repair through both homologous recombination and nonhomologous end joining. Mechanistically, DJ-1 interacts directly with PARP1, a nuclear enzyme essential for genomic stability, and stimulates its enzymatic activity during DNA repair. Importantly, cells from PD patients with the DJ-1 mutation also have defective PARP1 activity and impaired repair of DSBs. In summary, our findings uncover a novel function of nuclear DJ-1 in DNA repair and genome stability maintenance, and suggest that defective DNA repair may contribute to the pathogenesis of PD linked to DJ-1 mutations.

SUBMITTER: Wang ZX 

PROVIDER: S-EPMC10218208 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

Nuclear DJ-1 Regulates DNA Damage Repair via the Regulation of PARP1 Activity.

Wang Zhong-Xuan ZX   Liu Yi Y   Li Yao-Lin YL   Wei Qiao Q   Lin Rong-Rong RR   Kang Ruiqing R   Ruan Yang Y   Lin Zhi-Hao ZH   Xue Nai-Jia NJ   Zhang Bao-Rong BR   Pu Jia-Li JL  

International journal of molecular sciences 20230512 10


DNA damage and defective DNA repair are extensively linked to neurodegeneration in Parkinson's disease (PD), but the underlying molecular mechanisms remain poorly understood. Here, we determined that the PD-associated protein DJ-1 plays an essential role in modulating DNA double-strand break (DSB) repair. Specifically, DJ-1 is a DNA damage response (DDR) protein that can be recruited to DNA damage sites, where it promotes DSB repair through both homologous recombination and nonhomologous end joi  ...[more]

Similar Datasets

| S-EPMC11557828 | biostudies-literature
| S-EPMC9751128 | biostudies-literature
2024-09-16 | GSE271269 | GEO
| S-EPMC7486119 | biostudies-literature
| S-EPMC6895267 | biostudies-literature
2024-11-28 | PXD043522 | Pride
| S-EPMC3985661 | biostudies-literature
| S-EPMC3236618 | biostudies-literature
| S-EPMC8287952 | biostudies-literature
| S-EPMC7321228 | biostudies-literature