Cargando…

Protein Arginine Methyltransferase 1 Is Essential for the Meiosis of Male Germ Cells

Protein arginine methyltransferase 1 (PRMT1) is a major enzyme responsible for the formation of methylarginine in mammalian cells; however, its function in vivo is not well understood due to its early embryonic lethality in null mice exhibiting spontaneous DNA damage, cell cycle delays, and defects...

Descripción completa

Detalles Bibliográficos
Autores principales: Waseem, Sahar, Kumar, Sudeep, Lee, Kanghoon, Yoon, Byoung-Ha, Kim, Mirang, Kim, Hail, Lee, Keesook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348183/
https://www.ncbi.nlm.nih.gov/pubmed/34360715
http://dx.doi.org/10.3390/ijms22157951
_version_ 1783735277435486208
author Waseem, Sahar
Kumar, Sudeep
Lee, Kanghoon
Yoon, Byoung-Ha
Kim, Mirang
Kim, Hail
Lee, Keesook
author_facet Waseem, Sahar
Kumar, Sudeep
Lee, Kanghoon
Yoon, Byoung-Ha
Kim, Mirang
Kim, Hail
Lee, Keesook
author_sort Waseem, Sahar
collection PubMed
description Protein arginine methyltransferase 1 (PRMT1) is a major enzyme responsible for the formation of methylarginine in mammalian cells; however, its function in vivo is not well understood due to its early embryonic lethality in null mice exhibiting spontaneous DNA damage, cell cycle delays, and defects in check point activation. Here, we generated germ cell-specific Prmt1 knock-out (KO) mice to evaluate the function of PRMT1 in spermatogenesis. Our findings demonstrate that PRMT1 is vital for male fertility in mice. Spermatogenesis in Prmt1 KO mice was arrested at the zygotene-like stage of the first meiotic division due to an elevated number of DNA double-strand breaks (DSBs). There was a loss of methylation in meiotic recombination 11 (MRE11), the key endonuclease in MRE11/RAD50/NBS 1 (MRN) complex, resulting in the accumulation of SPO11 protein in DSBs. The ATM-mediated negative feedback control over SPO11 was lost and, consequently, the repair pathway of DSBs was highly affected in PRMT1 deficient male germ cells. Our findings provide a novel insight into the role of PRMT1-mediated asymmetric demethylation in mouse spermatogenesis.
format Online
Article
Text
id pubmed-8348183
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-83481832021-08-08 Protein Arginine Methyltransferase 1 Is Essential for the Meiosis of Male Germ Cells Waseem, Sahar Kumar, Sudeep Lee, Kanghoon Yoon, Byoung-Ha Kim, Mirang Kim, Hail Lee, Keesook Int J Mol Sci Article Protein arginine methyltransferase 1 (PRMT1) is a major enzyme responsible for the formation of methylarginine in mammalian cells; however, its function in vivo is not well understood due to its early embryonic lethality in null mice exhibiting spontaneous DNA damage, cell cycle delays, and defects in check point activation. Here, we generated germ cell-specific Prmt1 knock-out (KO) mice to evaluate the function of PRMT1 in spermatogenesis. Our findings demonstrate that PRMT1 is vital for male fertility in mice. Spermatogenesis in Prmt1 KO mice was arrested at the zygotene-like stage of the first meiotic division due to an elevated number of DNA double-strand breaks (DSBs). There was a loss of methylation in meiotic recombination 11 (MRE11), the key endonuclease in MRE11/RAD50/NBS 1 (MRN) complex, resulting in the accumulation of SPO11 protein in DSBs. The ATM-mediated negative feedback control over SPO11 was lost and, consequently, the repair pathway of DSBs was highly affected in PRMT1 deficient male germ cells. Our findings provide a novel insight into the role of PRMT1-mediated asymmetric demethylation in mouse spermatogenesis. MDPI 2021-07-26 /pmc/articles/PMC8348183/ /pubmed/34360715 http://dx.doi.org/10.3390/ijms22157951 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Waseem, Sahar
Kumar, Sudeep
Lee, Kanghoon
Yoon, Byoung-Ha
Kim, Mirang
Kim, Hail
Lee, Keesook
Protein Arginine Methyltransferase 1 Is Essential for the Meiosis of Male Germ Cells
title Protein Arginine Methyltransferase 1 Is Essential for the Meiosis of Male Germ Cells
title_full Protein Arginine Methyltransferase 1 Is Essential for the Meiosis of Male Germ Cells
title_fullStr Protein Arginine Methyltransferase 1 Is Essential for the Meiosis of Male Germ Cells
title_full_unstemmed Protein Arginine Methyltransferase 1 Is Essential for the Meiosis of Male Germ Cells
title_short Protein Arginine Methyltransferase 1 Is Essential for the Meiosis of Male Germ Cells
title_sort protein arginine methyltransferase 1 is essential for the meiosis of male germ cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348183/
https://www.ncbi.nlm.nih.gov/pubmed/34360715
http://dx.doi.org/10.3390/ijms22157951
work_keys_str_mv AT waseemsahar proteinargininemethyltransferase1isessentialforthemeiosisofmalegermcells
AT kumarsudeep proteinargininemethyltransferase1isessentialforthemeiosisofmalegermcells
AT leekanghoon proteinargininemethyltransferase1isessentialforthemeiosisofmalegermcells
AT yoonbyoungha proteinargininemethyltransferase1isessentialforthemeiosisofmalegermcells
AT kimmirang proteinargininemethyltransferase1isessentialforthemeiosisofmalegermcells
AT kimhail proteinargininemethyltransferase1isessentialforthemeiosisofmalegermcells
AT leekeesook proteinargininemethyltransferase1isessentialforthemeiosisofmalegermcells