PARP1 at the crossroad of cellular senescence and nucleolar processes

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.

Keywords: Cellular stress; Nucleolus; PARP1; Senescence.