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The Nup84 complex coordinates the DNA damage response to warrant genome integrity
Hélène Gaillard1, José M Santos-Pereira1, Andrés Aguilera1
1Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, 41092 Seville, Spain.
Nucleic Acids Research
|February 5, 2019
Summary
Nuclear pore complexes (NPCs) are crucial for DNA repair, specifically nucleotide excision repair (NER) and sister chromatid recombination (SCR). Their absence impairs DNA damage response, affecting replication and genome integrity.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- DNA lesions disrupt vital cellular processes like transcription and replication, necessitating efficient repair for genome stability.
- Nuclear pore complexes (NPCs), traditionally known for transport, also play roles in transcription, nuclear organization, and DNA double-strand break (DSB) repair.
Purpose of the Study:
- To investigate the role of the Nup84 nuclear pore component in DNA damage response and repair.
- To determine the impact of Nup84 absence on cellular sensitivity to UV radiation and replication fork progression.
Main Methods:
- Analysis of UV-induced DNA lesion removal by nucleotide excision repair (NER) in nup84Δ cells.
- Assessment of sensitivity to UV radiation during S phase and replication fork progression in nup84Δ cells.
- Evaluation of DNA double-strand break (DSB) repair via sister chromatid recombination (SCR) in nup84Δ cells.
Main Results:
- Nucleotide excision repair (NER) of UV-induced DNA lesions is impaired in the absence of Nup84.
- nup84Δ cells exhibit increased sensitivity to UV radiation in early S phase and delayed replication fork progression.
- Cells lacking Nup84 are deficient in repairing replication-associated DSBs through SCR and depend on post-replicative repair.
Conclusions:
- The NPC, specifically Nup84, plays a critical role in the DNA damage response.
- Nup84 facilitates replication through damaged DNA by promoting NER and SCR, thereby preventing genomic instability.
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