K6-linked SUMOylation of BAF regulates nuclear integrity and DNA replication in mammalian cells

Lin, Qiaoyu; Yu, Bin; Wang, Xiangyang; Zhu, Shicong; Zhao, Guoqing; Jia, Mingkang; Huang, Fan; Xu, Nan; Ren, He; Jiang, Qing; Zhang, Chuanmao

doi:10.1073/pnas.1912984117

Cited by 17 publications

(13 citation statements)

References 53 publications

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“…6 D and E). These results are consistent with previous findings to indicate that cGAS is active in the cytoplasm whereas nuclear cGAS is inactive (Kujirai et al, 2020;Michalski et al, 2020;Zhao et al, 2020). The accumulation levels of sfGFP-DARPin-LA6 and Halo-BAF at the rupture sites were lower in cells with nuclear cGAS-sfCherry compared to those with the cytoplasmic cGAS-sfCherry (Fig.…”

Section: Cytoplasmic Cgas Accumulates At the Rupture Sites And Affects Lc And Baf Accumulationsupporting

confidence: 93%

Nucleoplasmic Lamin C Rapidly Accumulates at Sites of Nuclear Envelope Rupture with BAF and cGAS

Kono

Adam

Reddy

et al. 2022

Preprint

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In mammalian cell nuclei, the nuclear lamina (NL) underlies the nuclear envelope (NE) to maintain nuclear structure. The nuclear lamins, the major structural components of the NL, are involved in the protection against NE rupture induced by mechanical stress. However, the specific role of the lamins in repair of NE ruptures has not been fully determined. Our analyses using immunofluorescence and live-cell imaging revealed that lamin C but not the other lamin isoforms rapidly accumulated at sites of NE rupture induced by laser microirradiation in mouse embryonic fibroblasts. The immunoglobulin-like fold domain and the NLS were required for the recruitment from the nucleoplasm to the rupture sites with the Barrier-to-autointegration factor (BAF). The accumulation of nuclear BAF and cytoplasmic cyclic GMP-AMP (cGAMP) synthase (cGAS) at the rupture sites was in part dependent on lamin A/C. These results suggest that nucleoplasmic lamin C, BAF and cGAS concertedly accumulate at sites of NE rupture for repair.

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Section: Cytoplasmic Cgas Accumulates At the Rupture Sites And Affects Lc And Baf Accumulationsupporting

confidence: 93%

Nucleoplasmic Lamin C Rapidly Accumulates at Sites of Nuclear Envelope Rupture with BAF and cGAS

Kono

Adam

Reddy

et al. 2022

Preprint

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“…It has been reported that LA and/or LC play a role in retaining BAF inside the nucleus ( Lin et al, 2020 ). Therefore, we examined if BAF localization is affected by depletion of specific lamins by staining endogenous BAF in WT, Lmna -KO, Lmnb1 -KO and Lmnb2 -KO MEFs using two different antibodies.…”

Section: Resultsmentioning

confidence: 99%

Nucleoplasmic lamin C rapidly accumulates at sites of nuclear envelope rupture with BAF and cGAS

Kono

Adam

Sato

et al. 2022

Journal of Cell Biology

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In mammalian cell nuclei, the nuclear lamina (NL) underlies the nuclear envelope (NE) to maintain nuclear structure. The nuclear lamins, the major structural components of the NL, are involved in the protection against NE rupture induced by mechanical stress. However, the specific role of the lamins in repair of NE ruptures has not been fully determined. Our analyses using immunofluorescence and live-cell imaging revealed that the nucleoplasmic pool of lamin C rapidly accumulated at sites of NE rupture induced by laser microirradiation in mouse embryonic fibroblasts. The accumulation of lamin C at the rupture sites required both the immunoglobulin-like fold domain that binds to barrier-to-autointegration factor (BAF) and a nuclear localization signal. The accumulation of nuclear BAF and cytoplasmic cyclic GMP-AMP synthase (cGAS) at the rupture sites was in part dependent on lamin A/C. These results suggest that nucleoplasmic lamin C, BAF, and cGAS concertedly accumulate at sites of NE rupture for rapid repair.

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“…In our previous studies on SENP3, we discovered a number of SUMOylation-regulated proteins that function in interphase cells (Han et al, 2010;Huang et al, 2009;Lao et al, 2018;Liu et al, 2020;Ren et al, 2014;Wang et al, 2016;Zhou et al, 2016). More recently, we also found that the SUMOylation-deSUMOylation cycle regulates the functions of barrier-to-autointegration factor (BAF) in nuclear integrity maintenance and DNA replication in mammalian cells (Lin et al, 2020). Here, as an extension of our previous work, we found that SENP3 and SENP5 impact mitotic progression via deSUMOylating AurA and spatiotemporally controlling its kinase activity for precise spindle assembly and maintenance of genomic stability.…”

Section: Introductionmentioning

confidence: 97%

SUMO proteases SENP3 and SENP5 spatiotemporally regulate the kinase activity of Aurora A

Lin

Huang

et al. 2021

Journal of Cell Science

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Precise chromosome segregation is mediated by a well-assembled mitotic spindle, which requires balance of the kinase activity of Aurora A (AurA). However, how this kinase activity is regulated remains largely unclear. Here, using in vivo and in vitro assays, we report that conjugation of SUMO2 with AurA at K258 in early mitosis promotes the kinase activity of AurA and facilitates the binding with its activator, Bora. Knockdown of the SUMO proteases SENP3 and SENP5 disrupted the deSUMOylation of AurA, leading to an increased kinase activity and abnormalities in spindle assembly and chromosomes segregation which could be rescued by suppressing the kinase activity of AurA. Collectively, these results demonstrate that SENP3 and SENP5 deSUMOylate AurA to render a spatiotemporal control on its kinase activity in mitosis.

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K6-linked SUMOylation of BAF regulates nuclear integrity and DNA replication in mammalian cells

Cited by 17 publications

References 53 publications

Nucleoplasmic Lamin C Rapidly Accumulates at Sites of Nuclear Envelope Rupture with BAF and cGAS

Nucleoplasmic Lamin C Rapidly Accumulates at Sites of Nuclear Envelope Rupture with BAF and cGAS

Nucleoplasmic lamin C rapidly accumulates at sites of nuclear envelope rupture with BAF and cGAS

SUMO proteases SENP3 and SENP5 spatiotemporally regulate the kinase activity of Aurora A

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