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Lamin A/C-Associated Proteins Are Required for Centromere Assembly
Lamin A/C-Associated Proteins Are Required for Centromere Assembly
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211153129
- ISBN
- 9798346875840
- DDC
- 574
- 서명/저자
- Lamin A/C-Associated Proteins Are Required for Centromere Assembly
- 발행사항
- [Sl] : Northwestern University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 123 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-06, Section: B.
- 주기사항
- Advisor: Varma, Dileep.
- 학위논문주기
- Thesis (Ph.D.)--Northwestern University, 2024.
- 초록/해제
- 요약Many lamin A-associated proteins (LAP's) that are key constituents of the nuclear envelope (NE), assemble at the "core" domains of chromosomes during NE reformation and mitotic exit. However, the identity and function of the chromosomal core domains remain ill-defined. Here, we show that a distinct section of the core domain overlaps with the centromeres/kinetochores of chromosomes during mitotic telophase. The core domain can thus be demarcated into a kinetochore proximal core (KPC) on one side of the segregated chromosomes and the kinetochore distal core (KDC) on the opposite side, close to the central spindle. Based on these findings, we tested whether centromere assembly is connected to NE reformation. We find that centromere assembly is markedly perturbed after inhibiting the function of lamin A protein and the core-localized LAPs, BAF and Emerin. We also find that the LAAPs exhibit multiple biochemical interactions with the centromere and inner kinetochore proteins. Consistent with this, normal mitotic progression and chromosome segregation was severely impeded after inhibiting LAP function. Intriguingly, the inhibition of centromere function also interferes with the assembly of LAP components at the core domain, suggesting a mutual dependence of LAP and centromeres for their assembly at the core domains. Finally, we find that the localization of key proteins involved in the centromeric loading of CENP-A, including the Mis18 complex and HJURP were markedly affected in LAP-inhibited cells. Our evidence points to a model where LAP assembly at the core domain serves a key function in loading new copies of centromeric proteins during or immediately after mitotic exit.
- 일반주제명
- Cellular biology
- 일반주제명
- Biochemistry
- 일반주제명
- Genetics
- 일반주제명
- Bioengineering
- 키워드
- Centromeres
- 키워드
- Kinetochores
- 키워드
- Mitosis
- 키워드
- Nuclear lamina
- 키워드
- Nuclear envelope
- 기타저자
- Northwestern University Driskill Graduate Training Program in Life Sciences
- 기본자료저록
- Dissertations Abstracts International. 86-06B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520250211153129
■006m o d
■007cr#unu||||||||
■020 ▼a9798346875840
■035 ▼a(MiAaPQ)AAI31767536
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aLanderos, Adriana Guevara.
■24510▼aLamin A/C-Associated Proteins Are Required for Centromere Assembly
■260 ▼a[Sl]▼bNorthwestern University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a123 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-06, Section: B.
■500 ▼aAdvisor: Varma, Dileep.
■5021 ▼aThesis (Ph.D.)--Northwestern University, 2024.
■520 ▼aMany lamin A-associated proteins (LAP's) that are key constituents of the nuclear envelope (NE), assemble at the "core" domains of chromosomes during NE reformation and mitotic exit. However, the identity and function of the chromosomal core domains remain ill-defined. Here, we show that a distinct section of the core domain overlaps with the centromeres/kinetochores of chromosomes during mitotic telophase. The core domain can thus be demarcated into a kinetochore proximal core (KPC) on one side of the segregated chromosomes and the kinetochore distal core (KDC) on the opposite side, close to the central spindle. Based on these findings, we tested whether centromere assembly is connected to NE reformation. We find that centromere assembly is markedly perturbed after inhibiting the function of lamin A protein and the core-localized LAPs, BAF and Emerin. We also find that the LAAPs exhibit multiple biochemical interactions with the centromere and inner kinetochore proteins. Consistent with this, normal mitotic progression and chromosome segregation was severely impeded after inhibiting LAP function. Intriguingly, the inhibition of centromere function also interferes with the assembly of LAP components at the core domain, suggesting a mutual dependence of LAP and centromeres for their assembly at the core domains. Finally, we find that the localization of key proteins involved in the centromeric loading of CENP-A, including the Mis18 complex and HJURP were markedly affected in LAP-inhibited cells. Our evidence points to a model where LAP assembly at the core domain serves a key function in loading new copies of centromeric proteins during or immediately after mitotic exit.
■590 ▼aSchool code: 0163.
■650 4▼aCellular biology
■650 4▼aBiochemistry
■650 4▼aGenetics
■650 4▼aBioengineering
■653 ▼aCentromeres
■653 ▼aKinetochores
■653 ▼aMitosis
■653 ▼aNuclear lamina
■653 ▼aNuclear envelope
■690 ▼a0379
■690 ▼a0202
■690 ▼a0487
■690 ▼a0369
■71020▼aNorthwestern University▼bDriskill Graduate Training Program in Life Sciences.
■7730 ▼tDissertations Abstracts International▼g86-06B.
■790 ▼a0163
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17165149▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
