Human REV3 DNA Polymerase Zeta Localizes to Mitochondria and Protects the Mitochondrial Genome

To date, mitochondrial DNA polymerase γ (POLG) is the only polymerase known to be present in mammalian mitochondria. A dogma in the mitochondria field is that there is no other polymerase present in the mitochondria of mammalian cells. Here we demonstrate localization of REV3 DNA polymerase in the m...

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Main Authors:	Singh, Bhupendra, Li, Xiurong, Owens, Kjerstin M., Vanniarajan, Ayyasamy, Liang, Ping, Singh, Keshav K.
Format:	Online
Language:	English
Published:	Public Library of Science 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604079/

id	pubmed-4604079
recordtype	oai_dc
spelling	pubmed-46040792015-10-20 Human REV3 DNA Polymerase Zeta Localizes to Mitochondria and Protects the Mitochondrial Genome Singh, Bhupendra Li, Xiurong Owens, Kjerstin M. Vanniarajan, Ayyasamy Liang, Ping Singh, Keshav K. Research Article To date, mitochondrial DNA polymerase γ (POLG) is the only polymerase known to be present in mammalian mitochondria. A dogma in the mitochondria field is that there is no other polymerase present in the mitochondria of mammalian cells. Here we demonstrate localization of REV3 DNA polymerase in the mammalian mitochondria. We demonstrate localization of REV3 in the mitochondria of mammalian tissue as well as cell lines. REV3 associates with POLG and mitochondrial DNA and protects the mitochondrial genome from DNA damage. Inactivation of Rev3 leads to reduced mitochondrial membrane potential, reduced OXPHOS activity, and increased glucose consumption. Conversely, inhibition of the OXPHOS increases expression of Rev3. Rev3 expression is increased in human primary breast tumors and breast cancer cell lines. Inactivation of Rev3 decreases cell migration and invasion, and localization of Rev3 in mitochondria increases survival and the invasive potential of cancer cells. Taken together, we demonstrate that REV3 functions in mammalian mitochondria and that mitochondrial REV3 is associated with the tumorigenic potential of cells. Public Library of Science 2015-10-13 /pmc/articles/PMC4604079/ /pubmed/26462070 http://dx.doi.org/10.1371/journal.pone.0140409 Text en © 2015 Singh et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Singh, Bhupendra Li, Xiurong Owens, Kjerstin M. Vanniarajan, Ayyasamy Liang, Ping Singh, Keshav K.
spellingShingle	Singh, Bhupendra Li, Xiurong Owens, Kjerstin M. Vanniarajan, Ayyasamy Liang, Ping Singh, Keshav K. Human REV3 DNA Polymerase Zeta Localizes to Mitochondria and Protects the Mitochondrial Genome
author_facet	Singh, Bhupendra Li, Xiurong Owens, Kjerstin M. Vanniarajan, Ayyasamy Liang, Ping Singh, Keshav K.
author_sort	Singh, Bhupendra
title	Human REV3 DNA Polymerase Zeta Localizes to Mitochondria and Protects the Mitochondrial Genome
title_short	Human REV3 DNA Polymerase Zeta Localizes to Mitochondria and Protects the Mitochondrial Genome
title_full	Human REV3 DNA Polymerase Zeta Localizes to Mitochondria and Protects the Mitochondrial Genome
title_fullStr	Human REV3 DNA Polymerase Zeta Localizes to Mitochondria and Protects the Mitochondrial Genome
title_full_unstemmed	Human REV3 DNA Polymerase Zeta Localizes to Mitochondria and Protects the Mitochondrial Genome
title_sort	human rev3 dna polymerase zeta localizes to mitochondria and protects the mitochondrial genome
description	To date, mitochondrial DNA polymerase γ (POLG) is the only polymerase known to be present in mammalian mitochondria. A dogma in the mitochondria field is that there is no other polymerase present in the mitochondria of mammalian cells. Here we demonstrate localization of REV3 DNA polymerase in the mammalian mitochondria. We demonstrate localization of REV3 in the mitochondria of mammalian tissue as well as cell lines. REV3 associates with POLG and mitochondrial DNA and protects the mitochondrial genome from DNA damage. Inactivation of Rev3 leads to reduced mitochondrial membrane potential, reduced OXPHOS activity, and increased glucose consumption. Conversely, inhibition of the OXPHOS increases expression of Rev3. Rev3 expression is increased in human primary breast tumors and breast cancer cell lines. Inactivation of Rev3 decreases cell migration and invasion, and localization of Rev3 in mitochondria increases survival and the invasive potential of cancer cells. Taken together, we demonstrate that REV3 functions in mammalian mitochondria and that mitochondrial REV3 is associated with the tumorigenic potential of cells.
publisher	Public Library of Science
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604079/
_version_	1613487567200583680

Human REV3 DNA Polymerase Zeta Localizes to Mitochondria and Protects the Mitochondrial Genome

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