자료유형  

 학위논문

Control Number  

0017165149

International Standard Book Number  

9798346875840

Dewey Decimal Classification Number  

574

Main Entry-Personal Name  

Landeros, Adriana Guevara.

Publication, Distribution, etc. (Imprint  

[S.l.] : Northwestern University., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

123 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-06, Section: B.

General Note  

Advisor: Varma, Dileep.

Dissertation Note  

Thesis (Ph.D.)--Northwestern University, 2024.

Summary, Etc.  

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.

Subject Added Entry-Topical Term  

Cellular biology.

Subject Added Entry-Topical Term  

Biochemistry.

Subject Added Entry-Topical Term  

Genetics.

Subject Added Entry-Topical Term  

Bioengineering.

Index Term-Uncontrolled  

Centromeres

Index Term-Uncontrolled  

Kinetochores

Index Term-Uncontrolled  

Mitosis

Index Term-Uncontrolled  

Nuclear lamina

Index Term-Uncontrolled  

Nuclear envelope

Added Entry-Corporate Name  

Northwestern University Driskill Graduate Training Program in Life Sciences

Host Item Entry  

Dissertations Abstracts International. 86-06B.

Electronic Location and Access  

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Control Number  

joongbu:655417