A role of human RNase P subunits, Rpp29 and Rpp21, in homology directed-repair of double-strand breaks

Abstract DNA damage response (DDR) is needed to repair damaged DNA for genomic integrity preservation. Defective DDR causes accumulation of deleterious mutations and DNA lesions that can lead to genomic instabilities and carcinogenesis. Identifying new players in the DDR, therefore, is essential to...

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Autores principales:	Enas R. Abu-Zhayia, Hanan Khoury-Haddad, Noga Guttmann-Raviv, Raphael Serruya, Nayef Jarrous, Nabieh Ayoub
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Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cc0874a55e194e5880efeaff330eb613
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spelling	oai:doaj.org-article:cc0874a55e194e5880efeaff330eb6132021-12-02T11:53:02ZA role of human RNase P subunits, Rpp29 and Rpp21, in homology directed-repair of double-strand breaks10.1038/s41598-017-01185-62045-2322https://doaj.org/article/cc0874a55e194e5880efeaff330eb6132017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01185-6https://doaj.org/toc/2045-2322Abstract DNA damage response (DDR) is needed to repair damaged DNA for genomic integrity preservation. Defective DDR causes accumulation of deleterious mutations and DNA lesions that can lead to genomic instabilities and carcinogenesis. Identifying new players in the DDR, therefore, is essential to advance the understanding of the molecular mechanisms by which cells keep their genetic material intact. Here, we show that the core protein subunits Rpp29 and Rpp21 of human RNase P complex are implicated in DDR. We demonstrate that Rpp29 and Rpp21 depletion impairs double-strand break (DSB) repair by homology-directed repair (HDR), but has no deleterious effect on the integrity of non-homologous end joining. We also demonstrate that Rpp29 and Rpp21, but not Rpp14, Rpp25 and Rpp38, are rapidly and transiently recruited to laser-microirradiated sites. Rpp29 and Rpp21 bind poly ADP-ribose moieties and are recruited to DNA damage sites in a PARP1-dependent manner. Remarkably, depletion of the catalytic H1 RNA subunit diminishes their recruitment to laser-microirradiated regions. Moreover, RNase P activity is augmented after DNA damage in a PARP1-dependent manner. Altogether, our results describe a previously unrecognized function of the RNase P subunits, Rpp29 and Rpp21, in fine-tuning HDR of DSBs.Enas R. Abu-ZhayiaHanan Khoury-HaddadNoga Guttmann-RavivRaphael SerruyaNayef JarrousNabieh AyoubNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Enas R. Abu-Zhayia Hanan Khoury-Haddad Noga Guttmann-Raviv Raphael Serruya Nayef Jarrous Nabieh Ayoub A role of human RNase P subunits, Rpp29 and Rpp21, in homology directed-repair of double-strand breaks
description	Abstract DNA damage response (DDR) is needed to repair damaged DNA for genomic integrity preservation. Defective DDR causes accumulation of deleterious mutations and DNA lesions that can lead to genomic instabilities and carcinogenesis. Identifying new players in the DDR, therefore, is essential to advance the understanding of the molecular mechanisms by which cells keep their genetic material intact. Here, we show that the core protein subunits Rpp29 and Rpp21 of human RNase P complex are implicated in DDR. We demonstrate that Rpp29 and Rpp21 depletion impairs double-strand break (DSB) repair by homology-directed repair (HDR), but has no deleterious effect on the integrity of non-homologous end joining. We also demonstrate that Rpp29 and Rpp21, but not Rpp14, Rpp25 and Rpp38, are rapidly and transiently recruited to laser-microirradiated sites. Rpp29 and Rpp21 bind poly ADP-ribose moieties and are recruited to DNA damage sites in a PARP1-dependent manner. Remarkably, depletion of the catalytic H1 RNA subunit diminishes their recruitment to laser-microirradiated regions. Moreover, RNase P activity is augmented after DNA damage in a PARP1-dependent manner. Altogether, our results describe a previously unrecognized function of the RNase P subunits, Rpp29 and Rpp21, in fine-tuning HDR of DSBs.
format	article
author	Enas R. Abu-Zhayia Hanan Khoury-Haddad Noga Guttmann-Raviv Raphael Serruya Nayef Jarrous Nabieh Ayoub
author_facet	Enas R. Abu-Zhayia Hanan Khoury-Haddad Noga Guttmann-Raviv Raphael Serruya Nayef Jarrous Nabieh Ayoub
author_sort	Enas R. Abu-Zhayia
title	A role of human RNase P subunits, Rpp29 and Rpp21, in homology directed-repair of double-strand breaks
title_short	A role of human RNase P subunits, Rpp29 and Rpp21, in homology directed-repair of double-strand breaks
title_full	A role of human RNase P subunits, Rpp29 and Rpp21, in homology directed-repair of double-strand breaks
title_fullStr	A role of human RNase P subunits, Rpp29 and Rpp21, in homology directed-repair of double-strand breaks
title_full_unstemmed	A role of human RNase P subunits, Rpp29 and Rpp21, in homology directed-repair of double-strand breaks
title_sort	role of human rnase p subunits, rpp29 and rpp21, in homology directed-repair of double-strand breaks
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/cc0874a55e194e5880efeaff330eb613
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A role of human RNase P subunits, Rpp29 and Rpp21, in homology directed-repair of double-strand breaks

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