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Impact of PARP1, PARP2 & PARP3 on the Base Excision Repair of Nucleosomal DNA
M M Kutuzov1,2, E A Belousova1,2, E S Ilina1
1Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences (ICBFM SB RAS), Novosibirsk, Russia.
Abstract:
DNA is constantly attacked by different damaging agents; therefore, it requires frequent repair. On the one hand, the base excision repair (BER) system is responsible for the repair of the most frequent DNA lesions. On the other hand, the formation of poly(ADP-ribose) is one of the main DNA damage response reactions that is catalysed by members of the PARP family. PARP1, which belongs to the PARP family and performs approximately 90% of PAR synthesis in cells, could be considered a main regulator of the BER process. Most of the experimental data concerning BER investigation have been obtained using naked DNA. However, in the context of the eukaryotic cell, DNA is compacted in the nucleus, and the lowest compaction level is represented by the nucleosome. Thus, the organization of DNA into the nucleosome impacts the DNA-protein interactions that are involved in BER processes. Poly(ADP-ribosyl)ation (PARylation) is thought to regulate the initiation of the BER process at the chromatin level. In this review, we focus on the mechanisms involved in BER in the nucleosomal context and the potential effect of PARylation, which is catalysed by DNA-dependent PARP1, PARP2 and PARP3 proteins, on this process.
Insights
DNA repair is crucial for cell survival. This review explores base excision repair (BER) within nucleosomes and how poly(ADP-ribosyl)ation (PARylation) regulates this vital DNA repair process.
Area of Science:
- Molecular Biology
- Biochemistry
- Genetics
Background:
- DNA is continuously damaged by various agents, necessitating efficient repair mechanisms.
- The Base Excision Repair (BER) pathway is critical for rectifying common DNA lesions.
- Poly(ADP-ribosyl)ation (PARylation), catalyzed by PARP enzymes, is a key DNA damage response.
Purpose of the Study:
- To review the mechanisms of BER within the nucleosomal context.
- To investigate the role of PARylation in regulating BER at the chromatin level.
Main Methods:
- Literature review focusing on BER and PARylation.
- Analysis of DNA-protein interactions in nucleosomal DNA.
Main Results:
- DNA organization into nucleosomes impacts BER efficiency.
- PARylation by PARP1, PARP2, and PARP3 is implicated in regulating BER initiation on chromatin.
Conclusions:
- Understanding BER in nucleosomes is essential for comprehending DNA repair in eukaryotes.
- PARylation emerges as a significant regulator of BER initiation within the chromatin structure.
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