title: Barrier-to-autointegration factor is required to segregate and enclose chromosomes within the nuclear envelope and assemble the nuclear lamina.
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.
authors.affiliation: Department of Genetics, Institute of Life Sciences, Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Margalit
authors.forename: Miriam
authors.initials: M
authors.lastname: Segura-Totten
authors.forename: Yosef
authors.initials: Y
authors.lastname: Gruenbaum
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Wilson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D002875:Chromosomes; D019084:Fluorescent Antibody Technique, Indirect; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid
references.citation: J Biol Chem. 2003 Feb 28;278(9):6969-75
references.pmid: 12493765
references.citation: Genes Dev. 2002 Mar 1;16(5):533-47
references.pmid: 11877373
references.citation: Mol Biol Cell. 1997 Sep;8(9):1751-62
references.pmid: 9307971
references.citation: J Cell Sci. 2001 Dec;114(Pt 24):4575-85
references.pmid: 11792822
references.citation: Trends Genet. 2001 Nov;17(11):633-6
references.pmid: 11672863
references.citation: J Cell Sci. 1999 Aug;112 ( Pt 15):2485-92
references.pmid: 10393804
references.citation: Genetics. 1974 May;77(1):71-94
references.pmid: 4366476
references.citation: EMBO J. 2001 Aug 15;20(16):4399-407
references.pmid: 11500367
references.citation: Dev Biol. 1996 Sep 15;178(2):472-83
references.pmid: 8812143
references.citation: J Cell Biol. 2002 Aug 5;158(3):475-85
references.pmid: 12163470
references.citation: J Cell Sci. 2002 Mar 1;115(Pt 5):923-9
references.pmid: 11870211
references.citation: Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10428-33
references.pmid: 15232008
references.citation: Cell. 1982 Oct;30(3):687-96
references.pmid: 7139712
references.citation: Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):8997-9002
references.pmid: 10908652
references.citation: Trends Cell Biol. 2004 May;14(5):261-6
references.pmid: 15130582
references.citation: Symp Soc Exp Biol. 2004;(56):329-39
references.pmid: 15565891
references.citation: J Biol Chem. 2002 Nov 8;277(45):43288-300
references.pmid: 12215455
references.citation: Nat Rev Mol Cell Biol. 2005 Jan;6(1):21-31
references.pmid: 15688064
references.citation: Dev Biol. 2003 Apr 1;256(1):173-86
references.pmid: 12654300
references.citation: J Cell Sci. 2003 Sep 15;116(Pt 18):3811-23
references.pmid: 12902403
references.citation: Genetics. 2001 Mar;157(3):1217-26
references.pmid: 11238406
references.citation: Dev Biol. 2001 Dec 1;240(1):77-91
references.pmid: 11784048
references.citation: J Biol Chem. 2001 Sep 28;276(39):36404-10
references.pmid: 11473126
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4598-603
references.pmid: 12684533
references.citation: Nat Cell Biol. 2004 Jan;6(1):31-7
references.pmid: 14688791
references.citation: Cell Cycle. 2004 Feb;3(2):212-7
references.pmid: 14712091
references.citation: Mol Biol Cell. 2000 Sep;11(9):3089-99
references.pmid: 10982402
references.citation: J Cell Sci. 2004 Dec 1;117(Pt 25):6117-28
references.pmid: 15546916
references.citation: Proc Natl Acad Sci U S A. 2004 May 4;101(18):6987-92
references.pmid: 15100407
references.citation: J Struct Biol. 2004 Jul;147(1):31-41
references.pmid: 15109603
references.citation: Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1528-33
references.pmid: 9465049
references.citation: J Struct Biol. 2002 Oct-Dec;140(1-3):232-40
references.pmid: 12490171
references.citation: Mol Biol Cell. 2000 Nov;11(11):3937-47
references.pmid: 11071918