Dynamic properties of nuclear lamins: lamin B is associated with sites of DNA replication.

Moir, Robert D.; Montag-Lowy, Michalle; Goldman, Robert D.

doi:10.1083/jcb.125.6.1201

Cited by 247 publications

(229 citation statements)

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“…The recent discovery that B-type lamins redistribute from the nuclear envelope to replication factories, in S-phase fibroblasts [23] has served to emphasise this role. It seems likely that a re-distribution of B-type lamins from the nuclear envelope to replication factories would require Lamin B was immunoisolated from quiescent and S-phase cultures of HDF which had been incubated in the presence of 32P i for 4 h, and separated by SDS-PAGE through 8% gels.…”

Section: Discussionmentioning

confidence: 99%

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S‐Phase phosphorylation of lamin B2

Kill

Hutchison

1995

FEBS Letters

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Lamin B2 modification in synchronously dividing populations of human diploid fibroblasts was determined by 2-dimensional gel electrophoresis and [32p]orthophosphate labelling. In quiescent (Go) and G1 cultures of HDF, lamin B 2 migrated as 2 spots on 2-dimensional gels. In contrast, in S-phase populations of HDF lamin 132 migrated as a single basic species. The level of lamin 8 2 phosphorylation was determined after immunoisolation from [32p]orthophosphate labelled cells. The results of these experiments indicated a 2-3-fold increase in the steady state level of lamin B 2 phosphorylation in S-phase HDF compared with Go HDF. Consistent with this evidence, tryptic peptide maps revealed the presence of a phosphopeptide in S-phase lamin B 2 which was absent from Go lamin 8 2. Since all of the phosphate incorporated into S-phase and Go lamin B 2 was recovered in serine residues we conclude that the S-phase specific phosphopeptide did not represent either of the cdc2 sites associated with entry nuclear lamina breakdown.

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Section: Discussionmentioning

confidence: 99%

“…Thus most sites of DNA replication are not in contact with the lamina. However, recent studies have shown that, during S-phase, B-type lamins re-distribute from the nuclear envelope to active sites of DNA replication [23] indicating a direct role for lamins in DNA synthesis.…”

Section: Introductionmentioning

confidence: 99%

S‐Phase phosphorylation of lamin B2

Kill

Hutchison

1995

FEBS Letters

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“…Internal type-A lamins have been reported in HeLa cells (Hozak et al, 1995) and in mammalian cells expressing lamin A-GFP fusion proteins (Broers et al, 1999). Type-A and type-B lamins are also seen as intranuclear foci in mammalian cultured cells (Bridger et al, 1993;Moir et al, 1994). These foci are thought to be intermediate stages of lamin processing, before their incorporation into the peripheral lamina (Goldman et al, 1992).…”

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confidence: 99%

Essential Roles forCaenorhabditis elegansLamin Gene in Nuclear Organization, Cell Cycle Progression, and Spatial Organization of Nuclear Pore Complexes

Ben-Shahar

Riemer

et al. 2000

MBoC

379

360

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Caenorhabditis elegans has a single lamin gene, designated lmn-1 (previously termed CeLam-1). Antibodies raised against the lmn-1 product (Ce-lamin) detected a 64-kDa nuclear envelope protein. Ce-lamin was detected in the nuclear periphery of all cells except sperm and was found in the nuclear interior in embryonic cells and in a fraction of adult cells. Reductions in the amount of Ce-lamin protein produce embryonic lethality. Although the majority of affected embryos survive to produce several hundred nuclei, defects can be detected as early as the first nuclear divisions. Abnormalities include rapid changes in nuclear morphology during interphase, loss of chromosomes, unequal separation of chromosomes into daughter nuclei, abnormal condensation of chromatin, an increase in DNA content, and abnormal distribution of nuclear pore complexes (NPCs). Under conditions of incomplete RNA interference, a fraction of embryos escaped embryonic arrest and continue to develop through larval life. These animals exhibit additional phenotypes including sterility and defective segregation of chromosomes in germ cells. Our observations show that lmn-1 is an essential gene in C. elegans, and that the nuclear lamins are involved in chromatin organization, cell cycle progression, chromosome segregation, and correct spacing of NPCs. INTRODUCTIONThe nuclear lamina is a filamentous meshwork that is present between the inner nuclear membrane and the peripheral chromatin. The inner nuclear membrane and the nuclear lamina are involved in organizing nuclear structure and regulating nuclear events. These include the organization of the higher order structure of chromatin and regulation of nuclear assembly and disassembly. The nuclear lamina is a primary target for caspases in apoptosis (reviewed in Goldberg et al., 1999b). Lamins are the major proteins of the nuclear lamina. They are classified as type-V intermediate filaments and are composed of an ␣-helical rod domain flanked by a short amino (head) and a long carboxy (tail) domains. The rod domain of lamins is 52-nm long and contains four ␣-helices, each composed of heptad repeats. Coiled-coil interactions and head-to-tail associations between lamin monomers form 10-to 200-nm thick lamin filaments (reviewed in Stuurman et al., 1998) In vivo, lamin filaments are closely associated with the chromatin fibers (Belmont et al., 1993). In vitro, lamins can bind interphase chromatin (Hoger et al., 1991;Yuan et al., 1991;Taniura et al., 1995;Ulitzur et al., 1997;Goldberg et al., 1999a), mitotic chromosomes (Glass and Gerace, 1990;Glass et al., 1993), or specific DNA sequences (Shoeman and Traub, 1990;Luderus et al., 1992;Luderus et al., 1994;Baricheva et al., 1996;Zhao et al., 1996). The binding site of vertebrate lamins to chromatin is localized to specific sequences in the tail domain and can be displaced with the core histones H2A and H2B (Taniura et al., 1995;Goldberg et al., 1999a).The composition of the nuclear lamina varies in different cell types and is under developmental regulation ...

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“…The B-type lamins are expressed in all mammalian cells and have been highly conserved during vertebrate evolution. The B-type lamins have been reported to participate in many functions within the cell nucleus, including DNA replication (21) and the formation of the mitotic spindle (22). Recently, both lamin B1 and lamin B2 have been shown to be important for neuronal migration within the developing brain (23)(24)(25)(26).…”

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Farnesylation of lamin B1 is important for retention of nuclear chromatin during neuronal migration

Jung¹,

Nobumori²,

Goulbourne³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The role of protein farnesylation in lamin A biogenesis and the pathogenesis of progeria has been studied in considerable detail, but the importance of farnesylation for the B-type lamins, lamin B1 and lamin B2, has received little attention. Lamins B1 and B2 are expressed in nearly every cell type from the earliest stages of development, and they have been implicated in a variety of functions within the cell nucleus. To assess the importance of protein farnesylation for B-type lamins, we created knock-in mice expressing nonfarnesylated versions of lamin B1 and lamin B2. Mice expressing nonfarnesylated lamin B2 developed normally and were free of disease. In contrast, mice expressing nonfarnesylated lamin B1 died soon after birth, with severe neurodevelopmental defects and striking nuclear abnormalities in neurons. The nuclear lamina in migrating neurons was pulled away from the chromatin so that the chromatin was left "naked" (free from the nuclear lamina). Thus, farnesylation of lamin B1-but not lamin B2-is crucial for brain development and for retaining chromatin within the bounds of the nuclear lamina during neuronal migration.genetically modified mouse models T he nuclear lamina is an intermediate filament meshwork that lies beneath the inner nuclear membrane. This lamina provides structural support for the nucleus and also interacts with nuclear proteins and chromatin, thereby affecting many functions within the cell nucleus (1, 2). In mammals, the main protein components of the nuclear lamina are lamins A and C (A-type lamins) and lamins B1 and B2 (B-type lamins).Both B-type lamins and prelamin A (the precursor of lamin A) terminate with a CaaX motif, which triggers three posttranslational modifications (3-5): farnesylation of the carboxyl-terminal cysteine (the "C" in the CaaX motif) (6), endoproteolytic cleavage of the last three amino acids (the -aaX) (7,8), and carboxyl methylation of the newly exposed farnesylcysteine (9, 10). Prelamin A undergoes a second endoproteolytic cleavage event, mediated by zinc metalloproteinase STE24 (ZMPSTE24), which removes 15 additional amino acids from the carboxyl terminus, including the farnesylcysteine methyl ester (11)(12)(13)(14). Lamins B1 and B2 do not undergo the second cleavage step and therefore retain their farnesyl lipid anchor.The discovery that Hutchinson-Gilford progeria syndrome (HGPS) is caused by a LMNA mutation yielding an internally truncated farnesyl-prelamin A (15) has focused interest in the farnesylation of nuclear lamins. This interest has been fueled by the finding that disease phenotypes in mouse models of HGPS could be ameliorated by blocking protein farnesylation with a protein farnesyltransferase inhibitor (FTI) (16)(17)(18)(19). Most recently, children with HGPS seemed to show a positive response to FTI treatment (20).The prospect of using an FTI to treat children with HGPS naturally raises the issue of the importance of protein farnesylation for lamin B1 and lamin B2. The B-type lamins are expressed in all mammalian cells and have been h...

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Dynamic properties of nuclear lamins: lamin B is associated with sites of DNA replication.

Cited by 247 publications

References 57 publications

S‐Phase phosphorylation of lamin B2

S‐Phase phosphorylation of lamin B2

Essential Roles forCaenorhabditis elegansLamin Gene in Nuclear Organization, Cell Cycle Progression, and Spatial Organization of Nuclear Pore Complexes

Farnesylation of lamin B1 is important for retention of nuclear chromatin during neuronal migration

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