دورية أكاديمية
أعرض في EDS

MCM8 interacts with DDX5 to promote R-loop resolution.

التفاصيل البيبلوغرافية
العنوان: MCM8 interacts with DDX5 to promote R-loop resolution.
المؤلفون: Wen C; State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, 250012, China.; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China.; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, China.; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, China.; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, China.; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250012, China.; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, China., Cao L; State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, 250012, China.; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China.; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, China.; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, China.; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, China.; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250012, China.; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, China., Wang S; State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, 250012, China.; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China.; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, China.; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, China.; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, China.; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250012, China.; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, China., Xu W; State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, 250012, China.; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China.; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, China.; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, China.; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, China.; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250012, China.; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, China., Yu Y; State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, 250012, China.; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China.; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, China.; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, China.; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, China.; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250012, China.; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, China., Zhao S; State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, 250012, China.; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China.; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, China.; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, China.; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, China.; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250012, China.; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, China., Yang F; Advanced Medical Research Institute, Meili Lake Translational Research Park, Cheeloo College of Medicine, Shandong University, Jinan, China.; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, 250012, China., Chen ZJ; State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, 250012, China.; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China.; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, China.; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, China.; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, China.; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250012, China.; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, China.; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China.; Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Zhao S; State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, 250012, China. shidouzhao@sdu.edu.cn.; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China. shidouzhao@sdu.edu.cn.; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, China. shidouzhao@sdu.edu.cn.; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, China. shidouzhao@sdu.edu.cn.; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, China. shidouzhao@sdu.edu.cn.; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250012, China. shidouzhao@sdu.edu.cn.; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, China. shidouzhao@sdu.edu.cn., Yang Y; State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, 250012, China. YangYJ0204@sdu.edu.cn.; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China. YangYJ0204@sdu.edu.cn.; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, China. YangYJ0204@sdu.edu.cn.; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, China. YangYJ0204@sdu.edu.cn.; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, China. YangYJ0204@sdu.edu.cn.; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250012, China. YangYJ0204@sdu.edu.cn.; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, China. YangYJ0204@sdu.edu.cn., Qin Y; State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, 250012, China. qinyingying@sdu.edu.cn.; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, China. qinyingying@sdu.edu.cn.; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, 250012, China. qinyingying@sdu.edu.cn.; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, China. qinyingying@sdu.edu.cn.; Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, China. qinyingying@sdu.edu.cn.; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250012, China. qinyingying@sdu.edu.cn.; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, 250012, China. qinyingying@sdu.edu.cn.
المصدر: The EMBO journal [EMBO J] 2024 Jul; Vol. 43 (14), pp. 3044-3071. Date of Electronic Publication: 2024 Jun 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8208664 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2075 (Electronic) Linking ISSN: 02614189 NLM ISO Abbreviation: EMBO J Subsets: MEDLINE
أسماء مطبوعة: Publication: 2024- : [London] : Nature Publishing Group
Original Publication: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982-
مواضيع طبية MeSH: DEAD-box RNA Helicases*/metabolism , DEAD-box RNA Helicases*/genetics , Genomic Instability* , Minichromosome Maintenance Proteins*/metabolism , Minichromosome Maintenance Proteins*/genetics , R-Loop Structures*/genetics, Animals ; Female ; Humans ; Male ; Mice ; DNA Damage ; Germ Cells/metabolism
مستخلص: MCM8 has emerged as a core gene in reproductive aging and is crucial for meiotic homologous recombination repair. It also safeguards genome stability by coordinating the replication stress response during mitosis, but its function in mitotic germ cells remains elusive. Here we found that disabling MCM8 in mice resulted in proliferation defects of primordial germ cells (PGCs) and ultimately impaired fertility. We further demonstrated that MCM8 interacted with two known helicases DDX5 and DHX9, and loss of MCM8 led to R-loop accumulation by reducing the retention of these helicases at R-loops, thus inducing genome instability. Cells expressing premature ovarian insufficiency-causative mutants of MCM8 with decreased interaction with DDX5 displayed increased R-loop levels. These results show MCM8 interacts with R-loop-resolving factors to prevent R-loop-induced DNA damage, which may contribute to the maintenance of genome integrity of PGCs and reproductive reserve establishment. Our findings thus reveal an essential role for MCM8 in PGC development and improve our understanding of reproductive aging caused by genome instability in mitotic germ cells.
(© 2024. The Author(s).)
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معلومات مُعتمدة: 2021YFC2700100,2022YFC2703800 MOST | National Key Research and Development Program of China (NKPs); 82125014 National Natural Science Foundation for Distinguished Young Scholars; 32170867,32370906,32200697 MOST | National Natural Science Foundation of China (NSFC); 82371645 MOST | National Natural Science Foundation of China (NSFC); 31988101 Basic Science Center Program of NSFC; ZR2021ZD33 Natural Science Foundation of Shandong Province for Grand Basic Projects; 2020ZLYS02 Shandong Provincial Key Research and Development Program; 2021-I2M-5-001 CAMS Innovation Fund for Medical Sciences; tsqn202211370 Taishan Scholars Program for Young Experts of Shandong Province; ZR2023JQ031 Natural Science Foundation of Shandong Province for distinguished young scholars
فهرسة مساهمة: Keywords: Fertility; Genome Stability; MCM8; Primordial Germ Cells; R-loop
المشرفين على المادة: EC 3.6.1.- (Ddx5 protein, mouse)
EC 3.6.4.13 (DEAD-box RNA Helicases)
EC 3.6.4.12 (Minichromosome Maintenance Proteins)
EC 3.6.4.12 (Mcm8 protein, mouse)
تواريخ الأحداث: Date Created: 20240610 Date Completed: 20240715 Latest Revision: 20240813
رمز التحديث: 20240813
مُعرف محوري في PubMed: PMC11251167
DOI: 10.1038/s44318-024-00134-0
PMID: 38858601
قاعدة البيانات: MEDLINE
الوصف
تدمد:1460-2075
DOI:10.1038/s44318-024-00134-0