PARP1 Regulates the Biogenesis and Activity of Telomerase Complex Through Modification of H/ACA-Proteins

Savelyev, N.V.; Shepelev, N.M.; Lavrik, O.I.; Rubtsova, M.P.; Dontsova, O.A.

Авторы: Savelyev Nikita V., Shepelev Nikita M., Lavrik Olga I., Rubtsova Maria P., Dontsova Olga A.
Журнал: Frontiers in Cell and Developmental Biology
Том: 9
Год издания: 2021
Издательство: Frontiers Media S.A.
Местоположение издательства: Lausanne, Switzerland
DOI: 10.3389/fcell.2021.621134
Аннотация: Poly(ADP-ribose) polymerase 1 (PARP1) is established as a key regulator of thecellular DNA damage response and apoptosis. In addition, PARP1 participates in theglobal regulation of DNA repair, transcription, telomere maintenance, and inflammationresponse by modulating various DNA-protein and protein-protein interactions. Recently,it was reported that PARP1 also influences splicing and ribosomal RNA biogenesis.The H/ACA ribonucleoprotein complex is involved in a variety of cellular processessuch as RNA maturation. It contains non-coding RNAs with specific H/ACA domainsand four proteins: dyskerin (DKC1), GAR1, NHP2, and NOP10. Two of these proteins,DKC1 and GAR1, are targets of poly(ADP-ribosyl)ation catalyzed by PARP1. The H/ACARNA-binding proteins are involved in the regulation of maturation and activity of thetelomerase complex, which maintains telomere length. In this study, we demonstratedthat of poly(ADP-ribosyl)ation influences on RNA-binding properties of DKC1 and GAR1and telomerase assembly and activity. Our data provide the evidence that poly(ADPribosyl)ation regulates telomerase complex assembly and activity, in turn regulatingtelomere length that may be useful for design and development of anticancer therapeuticapproaches that are based on the inhibition of PARP1 and telomerase activities.
Добавил в систему: Рубцова Мария Петровна

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