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PMID: 15728376 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Barrier-to-autointegration factor is required to segregate and enclose chromosomes within the nuclear envelope and assemble the nuclear lamina.

Margalit A, Segura-Totten M, Gruenbaum Y, Wilson KL

Abstract

Barrier-to-autointegration factor (BAF) binds dsDNA, LEM-domain proteins, and lamins. Caenorhabditis elegans BAF requires Ce-lamin and two LEM-domain proteins (Ce-emerin and Ce-MAN1) to localize during nuclear assembly. It was unknown whether Ce-lamin and LEM proteins, in turn, depend on Ce-BAF (mutually dependent structural roles). RNA interference-mediated down-regulation of Ce-BAF caused gross defects in chromosome segregation, chromatin decondensation, and mitotic progression as early as the two-cell stage, and embryos died at the approximately 100-cell stage. Nuclear pores reassembled, whereas Ce-lamin, Ce-emerin, and Ce-MAN1 bound chromatin but remained patchy and disorganized. The nuclear membranes formed but failed to enclose anaphase-bridged chromatin. Time-lapse imaging showed two phenotypes: anaphase-bridged chromatin that eventually resolved, and segregated chromatin that returned to the midzone. Thus, the assembly of BAF, lamins, and LEM-domain proteins is mutually dependent, and is required to capture segregated chromosomes within the nascent nuclear envelope. Embryos that escaped lethality by down-regulation of Ce-BAF grew into sterile adults with misplaced distal tip cells and gonads, further suggesting that mild postembryonic reductions in BAF disrupt tissue-specific functions.

MeSH Terms
Amino Acid Sequence Animals Caenorhabditis elegans/genetics Chromosomes Fluorescent Antibody Technique, Indirect Microscopy, Electron, Transmission Molecular Sequence Data RNA Interference Sequence Homology, Amino Acid
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Margalit Ayelet
Department of Genetics, Institute of Life Sciences, Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel.
Segura-Totten Miriam
Gruenbaum Yosef
Wilson Katherine L
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2005-03-01
Epub
2005-00-22
Pages
3290-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC552915
Subset
IM
Grants
NIGMS NIH HHS · R01 GM064535 · United States
NIGMS NIH HHS · R01 GM64535 · United States
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