Nuclear lamins: key regulators of nuclear structure and activities

Prokocimer, Miron; Davidovich, Maya; Nissim-Rafinia, Malka; Wiesel-Motiuk, Naama; Bar, Daniel; Barkan, Rachel; Meshorer, Eran; Gruenbaum, Yosef

doi:10.1111/j.1582-4934.2009.00676.x

Cited by 42 publications

(63 citation statements)

References 204 publications

(164 reference statements)

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“…4,5 Lamins are major components of the nuclear lamina, a filamentous meshwork underlying the inner nuclear membrane involved in nuclear shape, nuclear pore complex spacing and resistance to mechanical stress. Moreover, by their numerous interactions and nucleoplasmic localization in the nuclear matrix, lamins have been involved in many other major nuclear functions, including regulation of gene expression, chromatin organization and DNA replication and repair (for review, see Broers et al 6 and Prokocimer et al 7 ).…”

Section: Introductionmentioning

confidence: 99%

New ZMPSTE24 (FACE1) mutations in patients affected with restrictive dermopathy or related progeroid syndromes and mutation update

et al. 2013

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Restrictive dermopathy (RD) is a rare and extremely severe congenital genodermatosis, characterized by a tight rigid skin with erosions at flexure sites, multiple joint contractures, low bone density and pulmonary insufficiency generally leading to death in the perinatal period. RD is caused in most patients by compound heterozygous or homozygous ZMPSTE24 null mutations. This gene encodes a metalloprotease specifically involved in lamin A post-translational processing. Here, we report a total of 16 families for whom diagnosis and molecular defects were clearly established. Among them, we report seven new ZMPSTE24 mutations, identified in classical RD or Mandibulo-acral dysplasia (MAD) affected patients. We also report nine families with one or two affected children carrying the common, homozygous thymine insertion in exon 9 and demonstrate the lack of a founder effect. In addition, we describe several new ZMPSTE24 variants identified in unaffected controls or in patients affected with non-classical progeroid syndromes. In addition, this mutation update includes a comprehensive search of the literature on previously described ZMPSTE24 mutations and associated phenotypes. Our comprehensive analysis of the molecular pathology supported the general rule: complete loss-of-function of ZMPSTE24 leads to RD, whereas other less severe phenotypes are associated with at least one haploinsufficient allele.

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Section: Introductionmentioning

confidence: 99%

New ZMPSTE24 (FACE1) mutations in patients affected with restrictive dermopathy or related progeroid syndromes and mutation update

et al. 2013

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“…[6][7][8] Lamins A/C, B1 and B2 are the major constituents of the lamina, which lines the inner nuclear membrane and determines its shape and integrity. [9][10][11] Based on their localization at the nuclear periphery, lamins modulate gene expression either by interacting with chromatin or by sequestering transcription factors. Additionally, other roles for lamina in the control of mitosis, DNA replication or the DNA damage response have more recently emerged.…”

Section: Introductionmentioning

confidence: 99%

Oxydative stress alters nuclear shape through lamins dysregulation

Barascu

Chalony²,

Pennarun³

et al. 2012

Nucleus

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“…[11][12][13] The cellular mechanisms affected by these malignancy-associated alterations of A-type lamins are only beginning to be unraveled. 14 Alterations of telomere biology and defects in repair of DNA damage are among the leading causes for genomic instability, and clear contributors to aging and cancer phenotypes. Loss of telomere Extra viEw Extra viEw of telomere structure and function.…”

Section: Introductionmentioning

confidence: 99%

Loss of A-type lamins and genomic instability

González-Suárez¹,

Redwood²,

Gonzalo³

2009

Cell Cycle

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Research performed in the last few years has revealed important roles for the spatial and temporal organization of the genome on genome function and integrity. A challenge in the field is to determine the molecular mechanisms involved in the organization of genome function. A-type lamins, key structural components of the nucleus, have been implicated in the maintenance of nuclear architecture and chromatin structure. Interestingly, alterations of A-type lamins lead to defects in DNA replication and repair as well as gene transcription and silencing. Elucidating the functions of these proteins is a topical subject since alterations of A-type lamins are associated with a variety of human diseases, ranging from muscular dystrophies and premature aging syndromes to cancer. Here, we discuss novels roles for A-type lamins in the maintenance of telomere structure, length and function as well as in the stabilization of a key DNA damage response factor. These studies support the notion that increased genomic instability due to defects in telomere biology and DNA repair contribute to the pathogenesis of lamin-related diseases.

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Nuclear lamins: key regulators of nuclear structure and activities

Abstract: The nuclear lamina is a proteinaceous structure located underneath the inner nuclear membrane (INM) J. Cell. Mol. Med. Vol 13, No 6, 2009 pp. 1059-1085 © Jerusalem, Jerusalem 91904, Israel. Tel.: 972-2-6585995 Fax: 972-2-5637848 E-mail: gru@vms.huji.ac.il The lamin molecule (Fig. 1A)

Cited by 42 publications

References 204 publications

New ZMPSTE24 (FACE1) mutations in patients affected with restrictive dermopathy or related progeroid syndromes and mutation update

New ZMPSTE24 (FACE1) mutations in patients affected with restrictive dermopathy or related progeroid syndromes and mutation update

Oxydative stress alters nuclear shape through lamins dysregulation

Loss of A-type lamins and genomic instability

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