Open AccessO‐GlcNAcase is essential for embryonic development and maintenance of genomic stability
Author(s) -
Yang Yong Ryoul,
Song Minseok,
Lee Ho,
Jeon Yoon,
Choi EunJeong,
Jang HyunJun,
Moon Hyo Youl,
Byun HaYoung,
Kim EungKyun,
Kim Dae Hyun,
Lee Mi Nam,
Koh Ara,
Ghim Jaewang,
Choi Jang Hyun,
LeeKwon Whaseon,
Kim Kyong Tai,
Ryu Sung Ho,
Suh PannGhill
Publication year - 2012
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2012.00801.x
Subject(s) - biology , mitosis , cytokinesis , cell cycle , microbiology and biotechnology , downregulation and upregulation , cell growth , embryonic stem cell , endocrinology , medicine , genetics , cell , gene , cell division
Summary Dysregulation of O‐GlcNAc modification catalyzed by O‐GlcNAc transferase (OGT) and O‐GlcNAcase (OGA) contributes to the etiology of chronic diseases of aging, including cancer, cardiovascular disease, type 2 diabetes, and Alzheimer’s disease. Here we found that natural aging in wild‐type mice was marked by a decrease in OGA and OGT protein levels and an increase in O‐GlcNAcylation in various tissues. Genetic disruption of OGA resulted in constitutively elevated O‐GlcNAcylation in embryos and led to neonatal lethality with developmental delay. Importantly, we observed that serum‐stimulated cell cycle entry induced increased O‐GlcNAcylation and decreased its level after release from G2/M arrest, indicating that O‐GlcNAc cycling by OGT and OGA is required for precise cell cycle control. Constitutively, elevated O‐GlcNAcylation by OGA disruption impaired cell proliferation and resulted in mitotic defects with downregulation of mitotic regulators. OGA loss led to mitotic defects including cytokinesis failure and binucleation, increased lagging chromosomes, and micronuclei formation. These findings suggest an important role for O‐GlcNAc cycling by OGA in embryonic development and the regulation of the maintenance of genomic stability linked to the aging process.