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PARP1 at the crossroad of cellular senescence and nucleolar processes
Kinga Kołacz1, Agnieszka Robaszkiewicz2
1Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland; Bio-Med-Chem Doctoral School of the University of Lodz and Lodz Institutes of the Polish Academy of Sciences, University of Lodz, Banacha 12 /16, 90-237 Lodz, Poland.
Abstract:
Senescent cells that occur in response to telomere shortening, oncogenes, extracellular and intracellular stress factors are characterized by permanent cell cycle arrest, the morphological and structural changes of the cell that include the senescence-associated secretory phenotype (SASP) and nucleoli rearrangement. The associated DNA lesions induce DNA damage response (DDR), which activates the DNA repair protein - poly-ADP-ribose polymerase 1 (PARP1). This protein consumes NAD+ to synthesize ADP-ribose polymer (PAR) on its own protein chain and on other interacting proteins. The involvement of PARP1 in nucleoli processes, such as rRNA transcription and ribosome biogenesis, the maintenance of heterochromatin and nucleoli structure, as well as controlling the crucial DDR protein release from the nucleoli to nucleus, links PARP1 with cellular senescence and nucleoli functioning. In this review we describe and discuss the impact of PARP1-mediated ADP-ribosylation on early cell commitment to senescence with the possible role of senescence-induced PARP1 transcriptional repression and protein degradation on nucleoli structure and function. The cause-effect interplay between PARP1 activation/decline and nucleoli functioning during senescence needs to be studied in detail.
Insights
Poly(ADP-ribose) polymerase 1 (PARP1) plays a key role in cellular senescence by influencing nucleoli structure and function through ADP-ribosylation. Further research is needed to understand the PARP1-nucleoli interplay during senescence.
Area of Science:
- Cellular Biology
- Molecular Biology
- Aging Research
Background:
- Cellular senescence is a state of permanent cell cycle arrest triggered by various stressors.
- Senescent cells exhibit characteristic morphological changes and a senescence-associated secretory phenotype (SASP).
- DNA damage response (DDR) pathways are activated during senescence, involving proteins like PARP1.
Purpose of the Study:
- To review the impact of PARP1-mediated ADP-ribosylation on early cellular commitment to senescence.
- To discuss the role of PARP1 in nucleoli structure and function during senescence.
- To highlight the need for further investigation into the PARP1-nucleoli interplay in senescence.
Main Methods:
- Literature review of studies on PARP1, cellular senescence, and nucleoli.
- Analysis of the molecular mechanisms linking PARP1 activity to senescence.
- Discussion of the functional consequences of PARP1-mediated ADP-ribosylation in senescent cells.
Main Results:
- PARP1 activation is linked to DNA damage response and cellular senescence.
- PARP1 influences nucleoli processes including rRNA transcription, ribosome biogenesis, and heterochromatin maintenance.
- PARP1 activity impacts the release of DDR proteins from nucleoli to the nucleus.
Conclusions:
- PARP1-mediated ADP-ribosylation is crucial for early cell commitment to senescence.
- Senescence-induced PARP1 repression and degradation may affect nucleoli structure and function.
- The precise cause-effect relationship between PARP1 and nucleoli functioning in senescence requires detailed study.
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