Proteasome subunit α4s is essential for formation of spermatoproteasomes and histone degradation during meiotic DNA repair in spermatocytes
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved..
Meiosis, which produces haploid progeny, is critical to ensuring both faithful genome transmission and genetic diversity. Proteasomes play critical roles at various stages of spermatogenesis, including meiosis, but the underlying mechanisms remain unclear. The atypical proteasomes, which contain the activator PA200, catalyze the acetylation-dependent degradation of the core histones in elongated spermatids and DNA repair in somatic cells. We show here that the testis-specific proteasome subunit α4s/PSMA8 is essential for male fertility by promoting proper formation of spermatoproteasomes, which harbor both PA200 and constitutive catalytic subunits. Immunostaining of a spermatocyte marker, SYCP3, indicated that meiosis was halted at the stage of spermatocytes in the α4s-deficient testes. α4s stimulated the in vitro degradation of the acetylated core histones, instead of nonacetylated histones, by the PA200-proteasome. Deletion of α4s blocked degradation of the core histones at DNA damage loci in spermatocytes, leading to meiotic arrest at metaphase I. Thus, α4s is required for histone degradation at meiotic DNA damage loci, proper progression of meiosis, and fertility in males by promoting proper formation of spermatoproteasomes. These results are important for understanding male infertility and might provide potential targets for male contraception or treatment of male infertility.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:296 |
|---|---|
| Enthalten in: |
The Journal of biological chemistry - 296(2021) vom: 01. Jan., Seite 100130 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Zhang, Zi-Hui [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
α4s/PSMA8 |
|---|
| Anmerkungen: |
Date Completed 20.08.2021 Date Revised 29.02.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1074/jbc.RA120.016485 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM318284561 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM318284561 | ||
| 003 | DE-627 | ||
| 005 | 20240229233703.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1074/jbc.RA120.016485 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1311.xml |
| 035 | |a (DE-627)NLM318284561 | ||
| 035 | |a (NLM)33262216 | ||
| 035 | |a (PII)S0021-9258(20)00122-2 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Zhang, Zi-Hui |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Proteasome subunit α4s is essential for formation of spermatoproteasomes and histone degradation during meiotic DNA repair in spermatocytes |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 20.08.2021 | ||
| 500 | |a Date Revised 29.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Meiosis, which produces haploid progeny, is critical to ensuring both faithful genome transmission and genetic diversity. Proteasomes play critical roles at various stages of spermatogenesis, including meiosis, but the underlying mechanisms remain unclear. The atypical proteasomes, which contain the activator PA200, catalyze the acetylation-dependent degradation of the core histones in elongated spermatids and DNA repair in somatic cells. We show here that the testis-specific proteasome subunit α4s/PSMA8 is essential for male fertility by promoting proper formation of spermatoproteasomes, which harbor both PA200 and constitutive catalytic subunits. Immunostaining of a spermatocyte marker, SYCP3, indicated that meiosis was halted at the stage of spermatocytes in the α4s-deficient testes. α4s stimulated the in vitro degradation of the acetylated core histones, instead of nonacetylated histones, by the PA200-proteasome. Deletion of α4s blocked degradation of the core histones at DNA damage loci in spermatocytes, leading to meiotic arrest at metaphase I. Thus, α4s is required for histone degradation at meiotic DNA damage loci, proper progression of meiosis, and fertility in males by promoting proper formation of spermatoproteasomes. These results are important for understanding male infertility and might provide potential targets for male contraception or treatment of male infertility | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a DNA damage | |
| 650 | 4 | |a histone degradation | |
| 650 | 4 | |a meiosis | |
| 650 | 4 | |a proteasome | |
| 650 | 4 | |a spermatogenesis | |
| 650 | 4 | |a α4s/PSMA8 | |
| 650 | 7 | |a Histones |2 NLM | |
| 650 | 7 | |a Proteasome Endopeptidase Complex |2 NLM | |
| 650 | 7 | |a EC 3.4.25.1 |2 NLM | |
| 650 | 7 | |a Psma8 protein, mouse |2 NLM | |
| 650 | 7 | |a EC 3.4.25.1 |2 NLM | |
| 700 | 1 | |a Jiang, Tian-Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Lian-Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Wenhui |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yixun |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, Xiao-Bo |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of biological chemistry |d 1945 |g 296(2021) vom: 01. Jan., Seite 100130 |w (DE-627)NLM000004995 |x 1083-351X |7 nnns |
| 773 | 1 | 8 | |g volume:296 |g year:2021 |g day:01 |g month:01 |g pages:100130 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1074/jbc.RA120.016485 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 296 |j 2021 |b 01 |c 01 |h 100130 | ||