Title | K6-linked SUMOylation of BAF regulates nuclear integrity and DNA replication in mammalian cells |
Authors | Lin, Qiaoyu Yu, Bin Wang, Xiangyang Zhu, Shicong Zhao, Gan Jia, Mingkang Huang, Fan Xu, Nan Ren, He Jiang, Qing Zhang, Chuanmao |
Affiliation | Peking Univ, Coll Life Sci, Minist Educ, Key Lab Cell Proliferat & Differentiat, Beijing 100871, Peoples R China |
Keywords | TO-AUTOINTEGRATION FACTOR CYCLE PROGRESSION STRUCTURAL BASIS AURORA-B S-PHASE SUMO BARRIER ROLES LAMIN LAMINOPATHIES |
Issue Date | 12-May-2020 |
Publisher | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA |
Abstract | Barrier-to-autointegration factor (BAF) is a highly conserved protein in metazoans that has multiple functions during the cell cycle. We found that BAF is SUMOylated at K6, and that this modification is essential for its nuclear localization and function, including nuclear integrity maintenance and DNA replication. K6-linked SUMOylation of BAF promotes binding and interaction with lamin A/C to regulate nuclear integrity. K6-linked SUMOylation of BAF also supports BAF binding to DNA and proliferating cell nuclear antigen and regulates DNA replication. SENP1 and SENP2 catalyze the de-SUMOylation of BAF at K6. Disrupting the SUMOylation and de-SUMOylation cycle of BAF at K6 not only disturbs nuclear integrity, but also induces DNA replication failure. Taken together, our findings demonstrate that SUMOylation at K6 is an important regulatory mechanism that governs the nuclear functions of BAF in mammalian cells. |
URI | http://hdl.handle.net/20.500.11897/588979 |
ISSN | 0027-8424 |
DOI | 10.1073/pnas.1912984117 |
Indexed | SCI(E) PubMed Scopus |
Appears in Collections: | 生命科学学院 细胞增殖分化调控机理研究教育部重点实验室 |