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Article

Mechanisms of A-Type Lamin Targeting to Nuclear Ruptures Are Disrupted in LMNA- and BANF1-Associated Progerias

by 1,2 and 1,3,*
1
Enabling Technologies Group, Sanford Research, Sioux Falls, SD 57104, USA
2
Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA
3
Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD 57104, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Wolfram Antonin and Symeon Siniossoglou
Cells 2022, 11(5), 865; https://doi.org/10.3390/cells11050865
Received: 18 January 2022 / Revised: 23 February 2022 / Accepted: 28 February 2022 / Published: 2 March 2022
(This article belongs to the Special Issue Lipid and Protein Dynamics at the Nuclear Envelope)
Mutations in the genes LMNA and BANF1 can lead to accelerated aging syndromes called progeria. The protein products of these genes, A-type lamins and BAF, respectively, are nuclear envelope (NE) proteins that interact and participate in various cellular processes, including nuclear envelope rupture and repair. BAF localizes to sites of nuclear rupture and recruits NE-repair machinery, including the LEM-domain proteins, ESCRT-III complex, A-type lamins, and membranes. Here, we show that it is a mobile, nucleoplasmic population of A-type lamins that is rapidly recruited to ruptures in a BAF-dependent manner via BAF’s association with the Ig-like β fold domain of A-type lamins. These initially mobile lamins become progressively stabilized at the site of rupture. Farnesylated prelamin A and lamin B1 fail to localize to nuclear ruptures, unless that farnesylation is inhibited. Progeria-associated LMNA mutations inhibit the recruitment affected A-type lamin to nuclear ruptures, due to either permanent farnesylation or inhibition of BAF binding. A progeria-associated BAF mutant targets to nuclear ruptures but is unable to recruit A-type lamins. Together, these data reveal the mechanisms that determine how lamins respond to nuclear ruptures and how progeric mutations of LMNA and BANF1 impair recruitment of A-type lamins to nuclear ruptures. View Full-Text
Keywords: nuclear envelope; nuclear rupture; progeria; LMNA; lamin; HGPS; BAF; BANF1; NGPS nuclear envelope; nuclear rupture; progeria; LMNA; lamin; HGPS; BAF; BANF1; NGPS
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MDPI and ACS Style

Sears, R.M.; Roux, K.J. Mechanisms of A-Type Lamin Targeting to Nuclear Ruptures Are Disrupted in LMNA- and BANF1-Associated Progerias. Cells 2022, 11, 865. https://doi.org/10.3390/cells11050865

AMA Style

Sears RM, Roux KJ. Mechanisms of A-Type Lamin Targeting to Nuclear Ruptures Are Disrupted in LMNA- and BANF1-Associated Progerias. Cells. 2022; 11(5):865. https://doi.org/10.3390/cells11050865

Chicago/Turabian Style

Sears, Rhiannon M., and Kyle J. Roux. 2022. "Mechanisms of A-Type Lamin Targeting to Nuclear Ruptures Are Disrupted in LMNA- and BANF1-Associated Progerias" Cells 11, no. 5: 865. https://doi.org/10.3390/cells11050865

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