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自整合屏障因子是在核膜内分离和包裹染色体以及组装核纤层所必需的。

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

作者信息

Margalit Ayelet, Segura-Totten Miriam, Gruenbaum Yosef, Wilson Katherine L

机构信息

Department of Genetics, Institute of Life Sciences, Hebrew University of Jerusalem, Givat Ram, Jerusalem 91904, Israel.

出版信息

Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3290-5. doi: 10.1073/pnas.0408364102. Epub 2005 Feb 22.

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.

摘要

自身整合屏障因子(BAF)可结合双链DNA、LEM结构域蛋白和核纤层蛋白。秀丽隐杆线虫的BAF在核组装过程中需要Ce-核纤层蛋白以及两种LEM结构域蛋白(Ce-emerin和Ce-MAN1)来定位。此前尚不清楚Ce-核纤层蛋白和LEM蛋白反过来是否依赖于Ce-BAF(相互依赖的结构作用)。RNA干扰介导的Ce-BAF下调早在二细胞阶段就导致染色体分离、染色质解聚和有丝分裂进程出现严重缺陷,胚胎在大约100细胞阶段死亡。核孔重新组装,而Ce-核纤层蛋白、Ce-emerin和Ce-MAN1与染色质结合,但仍呈斑片状且无序。核膜形成,但未能包围后期桥接的染色质。延时成像显示出两种表型:最终得以解决的后期桥接染色质,以及回到中区的分离染色质。因此,BAF、核纤层蛋白和LEM结构域蛋白的组装是相互依赖的,并且是在新生核膜内捕获分离染色体所必需的。通过下调Ce-BAF而逃过致死性的胚胎发育成不育成虫,其远端末梢细胞和性腺位置异常,这进一步表明BAF在胚胎后期的轻度减少会破坏组织特异性功能。

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本文引用的文献

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The nuclear lamina comes of age.核纤层步入成熟阶段。
Nat Rev Mol Cell Biol. 2005 Jan;6(1):21-31. doi: 10.1038/nrm1550.
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