國立虎尾科技大學 |

Investigation of Nuclear Envelope-Associated Progeria Proteins During Nuclear Envelope Rupture.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Investigation of Nuclear Envelope-Associated Progeria Proteins During Nuclear Envelope Rupture./
Author:	Sears, Rhiannon Marie.
Description:	1 online resource (160 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 84-06, Section: B.
Contained By:	Dissertations Abstracts International84-06B.
Subject:	Cellular biology. -
Online resource:	click for full text (PQDT)
ISBN:	9798363500855

Investigation of Nuclear Envelope-Associated Progeria Proteins During Nuclear Envelope Rupture.
Sears, Rhiannon Marie.

Investigation of Nuclear Envelope-Associated Progeria Proteins During Nuclear Envelope Rupture. - 1 online resource (160 pages)

Source: Dissertations Abstracts International, Volume: 84-06, Section: B.

Thesis (Ph.D.)--University of South Dakota, 2022.

Includes bibliographical references

The nuclear envelope (NE) is a specialized extension of the endoplasmic reticulum critical for the proper protection and organization of the genome. This interphase-only structure is host to several proteins and their interacting constituents that have various and diverse cellular roles. Mutations in NE constituents are associated with several human diseases. A subset of these diseases, known as progeria syndromes, are characterized by the premature presentation of physiological aging in a variety of tissues. Mutations in the genes LMNA and BANF1, which encode the A-type lamins and barrier-to-autointegration factor (BAF), can lead to these multisystem progeroid diseases. Though the underlying mechanisms of disease are poorly understood, progeria patient-derived cells show evidence of NE disruptions that result in NE ruptures and the loss of proper nucleocytoplasmic compartmentalization. Previously, we showed BAF localizes to sites of nuclear rupture and is required for recruiting NE-repair machinery. Here, we show a mobile, nucleoplasmic population of A-type lamins is recruited to ruptures in a BAF-dependent manner via BAF's association with the Ig-like β fold domain. Furthermore, disease mutations in A-type lamins that disrupt their mobility and/or interaction with BAF also disrupt their ability to target to nuclear ruptures. Similarly, a progeric BAF is unable to recruit A-type lamins to ruptures despite being able to target to NE rupture sites itself. Further analyses of the lamin disease-associated mutants revealed functional discrepancies during the nuclear rupture process.These data show that disruption of BAF and A-type lamin interactions compromise lamin recruitment to NE ruptures and may alter the proper mechanisms needed for efficient NE rupture response and repair, potentially contributing to disease phenotypes. Collectively, the results of these studies illustrate the value in comparative studies between laminopathy-associated disease mutations, especially those that result in the same disease.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2024

Mode of access: World Wide Web

ISBN: 9798363500855Subjects--Topical Terms:

1148666
Cellular biology.
Subjects--Index Terms:

Barrier-to-autointegration factorIndex Terms--Genre/Form:

554714
Electronic books.

Investigation of Nuclear Envelope-Associated Progeria Proteins During Nuclear Envelope Rupture.
LDR:03476ntm a22004097 4500 001 1148144
005 20240916070011.5
006 m o d
007 cr bn ---uuuuu
008 250605s2022 xx obm 000 0 eng d
020 $a 9798363500855
035 $a (MiAaPQ)AAI29999575
035 $a AAI29999575
040 $a MiAaPQ $b eng $c MiAaPQ $d NTU
100 1 $a Sears, Rhiannon Marie. $3 1474054
245 1 0 $a Investigation of Nuclear Envelope-Associated Progeria Proteins During Nuclear Envelope Rupture.
264 0 $c 2022
300 $a 1 online resource (160 pages)
336 $a text $b txt $2 rdacontent
337 $a computer $b c $2 rdamedia
338 $a online resource $b cr $2 rdacarrier
500 $a Source: Dissertations Abstracts International, Volume: 84-06, Section: B.
500 $a Advisor: Roux, Kyle J.;Chandrasekar, Indra.
502 $a Thesis (Ph.D.)--University of South Dakota, 2022.
504 $a Includes bibliographical references
520 $a The nuclear envelope (NE) is a specialized extension of the endoplasmic reticulum critical for the proper protection and organization of the genome. This interphase-only structure is host to several proteins and their interacting constituents that have various and diverse cellular roles. Mutations in NE constituents are associated with several human diseases. A subset of these diseases, known as progeria syndromes, are characterized by the premature presentation of physiological aging in a variety of tissues. Mutations in the genes LMNA and BANF1, which encode the A-type lamins and barrier-to-autointegration factor (BAF), can lead to these multisystem progeroid diseases. Though the underlying mechanisms of disease are poorly understood, progeria patient-derived cells show evidence of NE disruptions that result in NE ruptures and the loss of proper nucleocytoplasmic compartmentalization. Previously, we showed BAF localizes to sites of nuclear rupture and is required for recruiting NE-repair machinery. Here, we show a mobile, nucleoplasmic population of A-type lamins is recruited to ruptures in a BAF-dependent manner via BAF's association with the Ig-like β fold domain. Furthermore, disease mutations in A-type lamins that disrupt their mobility and/or interaction with BAF also disrupt their ability to target to nuclear ruptures. Similarly, a progeric BAF is unable to recruit A-type lamins to ruptures despite being able to target to NE rupture sites itself. Further analyses of the lamin disease-associated mutants revealed functional discrepancies during the nuclear rupture process.These data show that disruption of BAF and A-type lamin interactions compromise lamin recruitment to NE ruptures and may alter the proper mechanisms needed for efficient NE rupture response and repair, potentially contributing to disease phenotypes. Collectively, the results of these studies illustrate the value in comparative studies between laminopathy-associated disease mutations, especially those that result in the same disease.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2024
538 $a Mode of access: World Wide Web
650 4 $a Cellular biology. $3 1148666
650 4 $a Molecular biology. $3 583443
650 4 $a Aging. $3 559847
653 $a Barrier-to-autointegration factor
653 $a Lamin
653 $a LMNA
653 $a Nuclear envelope
653 $a Nuclear rupture
653 $a Progeria
655 7 $a Electronic books. $2 local $3 554714
690 $a 0379
690 $a 0307
690 $a 0493
710 2 $a ProQuest Information and Learning Co. $3 1178819
710 2 $a University of South Dakota. $b Basic Biomedical Sciences. $3 1473982
773 0 $t Dissertations Abstracts International $g 84-06B.
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=29999575 $z click for full text (PQDT)