1022-7954/05/4103- © 2005 Pleiades Publishing, Inc.
Russian Journal of Genetics, Vol. 41, No. 3, 2005, pp. 221–226. From Genetika, Vol. 41, No. 3, 2005, pp. 293–298.
Original English Text Copyright © 2005 by N. Sjakste, T. Sjakste.
Nuclear matrix (NM) is the structural framework of
the nucleus that consists of the peripheral lamins and
pore complexes, an internal ribonucleic protein net-
work, and residual nucleoli. The NM contains proteins
that contribute to the preservation of nuclear shape and
its organization. Nuclear matrix was discovered more
than 50 years ago by Zbarsky . Ever since its struc-
ture and functions have been intensively studied.
Nuclear matrix enables spatial organization of DNA
replication, transcription and repair processes; it har-
bors numerous enzymes  and transcription factors
. Eventual role for nuclear matrix structures in dif-
ferent pathologies was intensively sought, results of the
early studies were reviewed previously [4, 5]. In the
recent years important role of the nuclear matrix pro-
teins in development of several diseases have been
revealed. Recent discoveries of hereditary diseases
caused by mutations in lamins demands for reconsider-
ation of the role of mutated nuclear matrix proteins in
hereditary diseases in general. Mutations in the genes
of numerous enzymes and transcription factors known
to be crucial for development of several genetic pathol-
ogies result in abnormal functions of the nuclear matrix
as above proteins appear to be constituents of the struc-
ture. The present review summarizes data on the role of
nuclear matrix proteins in pathogenesis of hereditary
diseases; cancer and related diseases will be reviewed
HEREDITARY DNA REPAIR DEFECTS
AND PREMATURE AGING SYNDROMES
Hereditary diseases coupled to decreased DNA
repair are caused by mutations in DNA repair enzymes
and some auxiliary proteins. Many of these proteins
make part of the nuclear matrix structures. For exam-
ple, the RecQ helicase family comprises a conserved
group of proteins implicated in several aspects of DNA
metabolism. Three of the family members are defective
in heritable diseases characterized by abnormal growth,
premature aging, and predisposition to malignancies.
These include the WRN and BLM gene products that
are defective in Werner and Bloom syndromes, disor-
ders which share many phenotypic and cellular charac-
teristics including spontaneous genomic instability.
Both proteins are found in the nuclear matrix; more-
over, they interact with each other. Functionally, BLM
inhibits the exonuclease activity of WRN . Some
authors admit interaction of BLM with the nuclear
matrix, but do not ﬁnd its interaction with WRN .
BLM localizes to promyelocytic leukemia protein
(PML) nuclear bodies, structures attached to the
nuclear matrix .
Nuclear Matrix Proteins and Hereditary Diseases*
and T. Sjakste
University of Latvia, Faculty of Medicine, Riga, LV1001 Latvia; e-mail: Nikolajs.Sjakste@lu.lv
Institute of Biology of the University of Latvia, Salaspils, LV2169 Latvia
Received May 11, 2004
—The review summarizes literature data on alterations of structure or expression of different nuclear
matrix proteins in hereditary syndromes. From the point of view of involvement of nuclear matrix proteins in
etiology and pathogenesis of the disease, hereditary pathologies can be classiﬁed in pathologies with pathogen-
esis associated with defects of nuclear matrix proteins and pathologies associated to changes of the nuclear
matrix protein spectrum. The ﬁrst group includes laminopathies, hereditary diseases with abnormal nuclear-
matrix associated proteins and triplet extension diseases associated with accumulation of abnormal proteins in
the nuclear matrix. Laminopathies are hereditary diseases coupled to structural defects of the nuclear lamina.
These diseases include Emery–Dreifuss muscular dystrophy, limb girdle muscular dystrophy, dilated cardiomy-
opathy (DCM) with conduction system disease, familial partial lipodystrophy (FPLD), autosomal recessive
axonal neuropathy (Charcot–Marie–Tooth disorder type 2, CMT2), mandibuloacral dysplasia (MAD), Hutchi-
son–Gilford progeria syndrome (HGS), Greenberg skeletal dysplasia, and Pelger–Huet anomaly (PHA). Most
of them are due to mutations in the lamin A/C gene, one—to mutations in emerin gene, some are associated
with mutations in Lamin B receptor gene. In Werner’s, Bloom’s, Cockayne’s syndromes, Fanconi anemia, mul-
tiple carboxylase deﬁciency mutations in nuclear matrix protein or enzyme gene lead to deﬁcient DNA repair,
abnormal regulation of cell growth and differentiation or other speciﬁc metabolic functions. Proteins with a
long polyglutamic tract synthesized in the cells of patients with dentato-rubral and pallido-luysian atrophy,
myotonic dystrophy and Huntington disease interfere with transcription on the nuclear matrix. Down’s syn-
drome is a representative of the group of diseases with altered nuclear matrix protein spectrum.
* This article was submitted by the authors in English.