Advances in Genome Science (2024)

Book Volume 1

Foreword

Page: i- (1)
Author: Erich Wanker
DOI: 10.2174/9781608051298113010001

Preface

Page: ii- (1)
Author: Christian Neri
DOI: 10.2174/9781608051298113010002

List of Contributors

Page: iii-ix (7)
Author: Christian Neri
DOI: 10.2174/9781608051298113010003

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Endometrial Cancer as a Familial Tumor: Pathology and Molecular Carcinogenesis

Page: 3-14 (12)
Author: Kouji Banno, Megumi Yanokura, Kennta Masuda, Arisa Ueki, Iori Kisu, Yusuke Kobayashi, Wataru Yamagami, Nobuyuki Susumu and Daisuke Aoki
DOI: 10.2174/9781608051298113010004

Abstract

Some cases of endometrial cancer are associated with a familial tumor and arereferred to as hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome). Suchtumors are thought to be induced by germline mutation of the DNA mismatch repair (MMR)gene, but many aspects of the pathology of familial endometrial cancer are unclear and noeffective screening method has been established. However, the pathology of endometrialcancer with familial tumor has been progressively clarified in recent studies. At present,about 0.5% of all cases of endometrial cancers meet the clinical diagnostic criteria forHNPCC. A recent analysis of the three MMR genes (hMLH1, hMSH2 and hMSH6) revealedgermline mutations in 18 of 120 cases (15.0%) of endometrial cancer with familialaccumulation of cancer or double cancer, with a frameshift mutation of the hMSH6 genebeing the most common. Many cases with mutation did not meet the current clinicaldiagnostic criteria for HNPCC, indicating that familial endometrial cancer is often notdiagnosed as HNPCC. The results suggest that the hMSH6 gene mutation may be importantin carcinogenesis in endometrial cancer and germline mutations of the MMR gene may bemore prevalent in cases associated with familial accumulation of cancer. An internationallarge-scale muticenter study is required to obtain further information about the pathology ofendometrial cancer as a familial tumor.

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Replication Origins and Timing of Temporal Replication in Budding Yeast: How to Solve the Conundrum?

Page: 15-44 (30)
Author: Matteo Barberis, Thomas W. Spiesser and Edda Klipp
DOI: 10.2174/9781608051298113010005

Abstract

Similarly to metazoans, the budding yeast Saccharomyces cereviasiae replicatesits genome with a defined timing. In this organism, well-defined, site-specific origins, areefficient and fire in almost every round of DNA replication. However, this strategy is neitherconserved in the fission yeast Saccharomyces pombe, nor in Xenopus or Drosophilaembryos, nor in higher eukaryotes, in which DNA replication initiates asynchronouslythroughout S phase at random sites. Temporal and spatial controls can contribute to thetiming of replication such as Cdk activity, origin localization, epigenetic status or geneexpression. However, a debate is going on to answer the question how individual origins areselected to fire in budding yeast. Two opposing theories were proposed: the “repliconparadigm” or “temporal program” vs. the “stochastic firing”. Recent data support thetemporal regulation of origin activation, clustering origins into temporal blocks of early andlate replication. Contrarily, strong evidences suggest that stochastic processes acting onorigins can generate the observed kinetics of replication without requiring a temporal order.In mammalian cells, a spatiotemporal model that accounts for a partially deterministic andpartially stochastic order of DNA replication has been proposed. Is this strategy the solutionto reconcile the conundrum of having both organized replication timing and stochastic originfiring also for budding yeast? In this review we discuss this possibility in the light of ourrecent study on the origin activation, suggesting that there might be a stochastic componentin the temporal activation of the replication origins, especially under perturbed conditions.

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The Role of Androgen Receptor Mutations in Progression of Prostate Cancer

Page: 45-65 (21)
Author: G.N. Brooke, J. Waxman and C. L. Bevan
DOI: 10.2174/9781608051298113010006

Abstract

Prostate cancer growth is regulated by the androgen receptor pathway and sotherapies to block androgen production and action are commonly used for the treatmentof this disease. Although initially successful in the majority of patients, resistance tohormonal therapy generally emerges and patients’ tumours progress to the ‘castrateresistant’ phase, for which few therapeutic options exist. Expression of the androgenreceptor is maintained in castrate resistant prostate cancer and there is a significant bodyof evidence that demonstrates that the androgen receptor is driving growth, even in theandrogen-depleted environment. Several mechanisms have been described to explainhow the androgen receptor is active under such circ*mstances and this current reviewsummarises how mutations of the androgen receptor provide a growth advantagethrough mechanisms that may involve cofactor recruitment, reduced ligand specificityor promoting constitutive activity. Indivividual mutations appear to differentiallyregulate gene expression, therefore tumours may behave differently dependent uponwhich mutation is present and which ligand is driving growth.

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open access plus

MUTYH Associated Polyposis (MAP)

Page: 66-100 (35)
Author: M.L.M. Binderup and M.L. Bisgaard
DOI: 10.2174/9781608051298113010007

Abstract

MUTYH Associated Polyposis (MAP) is an autosomal recessive predispositionto polyposis and colorectal cancer (CRC) caused by biallelic mutations in the base excisionrepair (BER) gene MUTYH. Phenotypically, MAP is difficult to distinguish from otherhereditary CRC syndromes like Familial Adenomatous Polyposis (FAP) and to a lesserextent Hereditary Non-Polyposis Colorectal Cancer (HNPCC), known to be caused bygermline mutations in the APC and Mismatch Repair (MMR) genes, respectively. Here wereview the main genetic and clinical aspects of MAP and aim to provide a broad, up-to-dateoverview of existing findings regarding MAP.

The exact role of MUTYH in CRC tumorgenesis is not fully determined, but a defective BERsystem due to germline MUTYH mutations leads to somatic mutations in the APC gene.Furthermore, cooperation between the BER and MMR systems exists, and possiblymonoallelic defects in both pathways are of significance to CRC development. The two mostcommon MUTYH variants, Y179C and G396D, both generate dysfunctional gene products,but Y179C has the most severe functional consequences and possibly causes a more severephenotype.

Median clinical onset of MAP is 47 years of age, and due to the recessive mode of inheritance,most have already developed CRC. Typically MAP patients develop between 10-100colorectal adenomas, although polyposis may not be obligatory for MAP. Typical FAP andHNPCC associated extracolonic manifestations are not common in MAP, except for uppergastro-duodenal polyposis which can be part of the phenotype, but more seldom than in FAP.Recommended MAP surveillance is colonoscopy with polypectomy from 20-25 years of age.In the future, genetic testing as well as surveillance may be targeted according to specific ethnicMUTYH mutation variants and genotype-phenotype correlations.

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Gene Clusters, Molecular Evolution and Disease: A Speculation

Page: 101-145 (45)
Author: Alireza Baradaran-Heravi, Leah I. Elizondo and Cornelius F. Boerkoel
DOI: 10.2174/9781608051298113010008

Abstract

Traditionally eukaryotic genes are considered independently expressed under thecontrol of their promoters and cis-regulatory domains. However, recent studies in worms,flies, mice and humans have shown that genes co-habiting a chromatin domain or “genomicneighborhood” are frequently co-expressed. Often these co-expressed genes neitherconstitute part of an operon nor function within the same biological pathway. Themechanisms underlying the partitioning of the genome into transcriptional genomicneighborhoods are poorly defined. However, cross-species analyses find that the linkageamong the co-expressed genes of these clusters is significantly conserved and that theexpression patterns of genes within clusters have co-evolved with the clusters. Suchselection could be mediated by chromatin interactions with the nuclear matrix andlong-range remodeling of chromatin structure. In the context of human disease, we proposethat dysregulation of gene expression across genomic neighborhoods will cause highlypleiotropic diseases. Candidate genomic neighborhood diseases include the nuclearlaminopathies, chromosomal translocations and genomic instability disorders, imprintingdisorders of errant insulator function, syndromes from impaired cohesin complex assembly,as well as diseases of global covalent histone modifications and DNA methylation. Thealteration of transcriptional genomic neighborhoods provides a model for studyingepigenetic alterations as quantitative traits in complex common human diseases.

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Expression and Function of Kruppel Like-Factors (KLF) in Carcinogenesis

Page: 146-168 (23)
Author: Diab Thoria, Bureau Christophe, Hanoun Naima, Torrisani Jérôme, Vinel Jean-Pierre, Buscail Louis and Cordelier Pierre
DOI: 10.2174/9781608051298113010009

Abstract

Krüppel-like factor (KLF) family members share a three C2H2 zinc fingerDNA binding domain, and are involved in cell proliferation and differentiation control innormal as in pathological situations. Studies over the past several years support asignificant role for this family of transcription factors in carcinogenesis. KLFs can bothactivate and repress genes that participate in cell-cycle regulation. Among them, manyup-regulated genes are inhibitors of proliferation, whereas genes that promote cellproliferation are repressed. However, several studies do present KLFs as positiveregulator of cell proliferation. KLFs can be deregulated in multiple cancers either by lossof heterozygosity (LOH), somatic mutation or transcriptional silencing by promoterhypermethylation. Accordingly, KLF mediates growth inhibition when ectopicallyexpressed in multiple cancer-derived cell lines through the inhibition of a number of keyoncogenic signalling pathways, and to reverse the tumorogenic phenotype in vivo. Takentogether, these observations suggest that KLFs act as tumor suppressor. However, insome occasion, KLFs could act as tumor promoters, depending on “cellular context”.Thus, this review will discuss the roles and the functions of KLF family members incarcinogenesis, with a special focus on cancers from epithelial origin.

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Episcopic 3D Imaging Methods: Tools for Researching Gene Function

Page: 169-188 (20)
Author: Wolfgang J. Weninger and Stefan H. Geyer
DOI: 10.2174/9781608051298113010010

Abstract

This work aims at describing episcopic 3D imaging methods and at discussing howthese methods can contribute to researching the genetic mechanisms driving embryogenesisand tissue remodelling, and the genesis of pathologies. Several episcopic 3D imaging methodsexist. The most advanced are capable of generating high-resolution volume data (voxel sizesfrom 0.5x0.5x1μm3 upwards) of small to large embryos of model organisms and tissuesamples. Beside anatomy and tissue architecture, gene expression and gene product patternscan be three dimensionally analyzed in their precise anatomical and histological context withthe aid of whole mount in situ hybridization or whole mount immunohistochemical stainingtechniques. Episcopic 3D imaging techniques were and are employed for analyzing the precisemorphological phenotype of experimentally malformed, randomly produced, or geneticallyengineered embryos of biomedical model organisms. It has been shown that episcopic 3Dimaging also fits for describing the spatial distribution of genes and gene products duringembryogenesis, and that it can be used for analyzing tissue samples of adult model animals andhumans. The latter offers the possibility to use episcopic 3D imaging techniques forresearching the causality and treatment of pathologies or for staging cancer. Such applications,however, are not yet routine and currently only preliminary results are available. We concludethat, although episcopic 3D imaging is in its very beginnings, it represents an upcomingmethodology, which in short terms will become an indispensable tool for researching thegenetic regulation of embryo development as well as the genesis of malformations anddiseases.

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Drosophila Lethal Giant Larvae Neoplastic Mutant as a Genetic Tool for Cancer Modelling

Page: 189-209 (21)
Author: Francesca Froldi, Marcello Ziosi, Annalisa Pession and Daniela Grifoni
DOI: 10.2174/9781608051298113010011

Abstract

Drosophila lethal giant larvae (lgl) is a tumour suppressor gene whose function inestablishing apical-basal cell polarity as well as in exerting proliferation control in epithelialtissues is conserved between flies and mammals. Individuals bearing lgl null mutations showa gradual loss of tissue architecture and an extended larval life in which cell proliferationnever ceases and no differentiation occurs, resulting in prepupal lethality. When tissues fromthose individuals are transplanted into adult normal recipients, a subset of cells, possibly thecancer stem cells, are able to proliferate and migrate to distant sites forming metastases whicheventually kill the host. This phenotype closely resembles that of mammalian epithelialcancers, in which loss of cell polarity is one of the hallmarks of a malignant, metastaticbehaviour associated with poor prognosis. Lgl protein shares with its human counterpartHuman giant larvae-1 (Hugl-1) significant stretches of sequence similarity that wedemonstrated to translate into a complete functional conservation, pointing out a role in cellproliferation control and tumourigenesis also for the human hom*ologue. The functionalconservation and the power of fly genetics, that allows the researcher to manipulate the flygenome at a level of precision that exceeds that of any other multicellular genetic system,make this Drosophila mutant a very suitable model in which to investigate the mechanismsunderlying epithelial tumour formation, progression and metastatisation. In this review, wewill summarise the results obtained in the last years using this model for the study of cancerbiology. Moreover, we will discuss how recent advances in developmental geneticstechniques have succeeded in enhancing the similarities between fly and humantumourigenesis, giving Drosophila a pivotal role in the study of such a complex geneticdisease.

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Genetic Insights Through Genome Wide Association Studies in Type 2 Diabetes Mellitus will Lead to New Therapeutics

Page: 210-240 (31)
Author: Marcel G. M. Wolfs, Naishi Li, Jingyuan Fu, Cisca Wijmenga, Timon W. van Haeften and Marten H. Hofker
DOI: 10.2174/9781608051298113010012

Abstract

Type 2 diabetes is a disorder of dysregulated glucose homeostasis. Normalglucose homeostasis is a complex process involving several interacting mechanisms,such as insulin secretion, insulin sensitivity, glucose production, and glucose uptake. Thedysregulation of one or more of these mechanisms due to environmental and/or geneticfactors, can lead to a defective glucose homeostasis. Hyperglycemia is managed byaugmenting insulin secretion and/or interaction with hepatic glucose production, as wellas by decreasing dietary caloric intake and raising glucose metabolism through exercise.Although these interventions can delay disease progression and correct blood glucoselevels, they are not able to cure the disease or stop its progression entirely. Bettermanagement of type 2 diabetes is sorely needed. Advances in genotyping techniques andthe availability of large patient cohorts have made it possible to identify common geneticvariants associated with type 2 diabetes through genome-wide association studies(GWAS). So far, genetic variants on 50 loci have been identified. Most of these locicontain or lie close to genes that were not previously linked to diabetes and they may thusharbor targets for new drugs. It is also hoped that further genetic studies will pave the wayfor predictive genetic screening. The newly discovered candidate genes for type 2diabetes can be classified based on their presumed molecular function, and we discuss therelation between these gene classes and current treatments. We go on to consider whetherthe new genes provide opportunities for developing alternative drug therapies.

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Indispensable Roles of Plastids in Arabidopsis thaliana Embryogenesis – Update

Page: 241-260 (20)
Author: Mehdi Nafati and Kentaro Inoue
DOI: 10.2174/9781608051298113010013

Abstract

The plastid is an organelle vital to all photosynthetic and some nonphotosyntheticeukaryotes. Although the plastid has its own genome, more than 95% ofproteins in this organelle are encoded in the nucleus, representing slightly lower than10% of all the nuclear-encoded proteins in the model plant Arabidopsis thaliana. Recentfunctional genomic and molecular genetic studies have shown that ca. 400 nonredundantnuclear genes are required for proper embryo formation of A. thaliana, andthat more than one third of them encode plastid-localized proteins. Classification ofthese genes based on terminal phenotypes of knockout mutants has revealed that nonphotosyntheticmetabolic activity of plastids is a prerequisite for the transition ofpreglobular to globular embryos, and that plastid gene expression becomes significant ator after the globular stage. Functions of the products of 28 out of 105 genes shown to berequired for embryo development at the globular and later stages remain unknown.Several approaches to address this issue are discussed.

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Mass Spectrometry-Based Approaches Toward Absolute Quantitative Proteomics

Page: 261-292 (32)
Author: Keiji Kito and Takashi Ito
DOI: 10.2174/9781608051298113010014

Abstract

Mass spectrometry has served as a major tool for the discipline of proteomicsto catalogue proteins in an unprecedented scale. With chemical and metabolic techniquesfor stable isotope labeling developed over the past decade, it is now routinely used as amethod for relative quantification to provide valuable information on alteration of proteinabundance in a proteome-wide scale. Recently, absolute or stoichiometric quantificationof proteome is becoming feasible, in particular, with the development of strategies withisotope-labeled standards composed of concatenated peptides. On the other hand,remarkable progress has been also made in label-free quantification methods based on thenumber of identified peptides. Here we review these mass spectrometry-basedapproaches for absolute quantification of proteome and discuss their implications.

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Regulation of Interactions with Sliding Clamps During DNA Replication and Repair

Page: 293-315 (23)
Author: Francisco J. López de Saro
DOI: 10.2174/9781608051298113010015

Abstract

The molecular machines that replicate the genome consist of many interactingcomponents. Essential to the organization of the replication machinery are ring-shapedproteins, like the prokaryotic β-clamp or eukaryotic PCNA (Proliferating Cell NuclearAntigen), collectively named sliding clamps. They encircle the DNA molecule and slide onit freely and bidirectionally. Sliding clamps are typically associated to DNA polymerasesand provide these enzymes with the processivity required to synthesize large chromosomes.Additionally, they interact with a large array of proteins that perform enzymatic reactionson DNA, targeting and orchestrating their functions. In recent years there have been a largenumber of studies that have analyzed the structural details of how sliding clamps interactwith their ligands. However, much remains to be learned in relation to how theseinteractions are regulated to occur coordinately and sequentially. Since sliding clampsparticipate in reactions in which many different enzymes bind and then release from theclamp in an orchestrated way, it is critical to analyze how these changes in affinity takeplace. In this review I focus the attention on the mechanisms by which various types ofenzymes interact with sliding clamps and what is known about the regulation of thisbinding. Especially I describe emerging paradigms on how enzymes switch places onsliding clamps during DNA replication and repair of prokaryotic and eukaryotic genomes.

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Revealing Gene Function and Genetic Diversity in Plants and Animals via TILLING and EcoTILLING

Page: 316-351 (36)
Author: N.A. Barkley and M.L. Wang
DOI: 10.2174/9781608051298113010016

Abstract

With the fairly recent advent of inexpensive, rapid sequencing technologiesthat continues to improve sequencing efficiency and accuracy, many species of animals,plants, and microbes have complete annotated genome information publicly available.The focus on genomics has thus been shifting from the collection of whole sequencedgenomes to the study of functional genomics. Reverse genetic approaches have been usedfor many years to elucidate the gene function and resulting phenotype from DNAsequence content. Many of the currently used approaches (RNAi, gene knockout,site-directed mutagenesis, transposon tagging) rely on the creation of transgenic material,the development of which is not always feasible for many plant or animal species.TILLING is a non-transgenic reverse genetics approach that is applicable to all animaland plant species which can be mutagenized, regardless of its mating / pollinating system,ploidy level, or genome size. This approach, however, does require prior DNA sequenceinformation. TILLING can ultimately provide an allelic series of silent, missense,nonsense, and splice site mutations to examine the effect of various mutations in a geneand their link to a particular phenotype. TILLING has proven to be a practical, efficient,and an effective approach for functional genomic studies in numerous plant and animalspecies. EcoTILLING, which is a variant of TILLING, examines natural geneticvariation in populations and has been successfully utilized in animals and plants to revealgenetic diversity. In this review, TILLING and EcoTILLING techniques are describedand reviewed, as well as, their beneficial applications and limitations.

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Variations Around the Arrestin Fold

Page: 352-376 (25)
Author: Laurence Aubry, Dorian Guetta and Gérard Klein
DOI: 10.2174/9781608051298113010017

Abstract

Endocytosis of ligand-activated plasma membrane receptors has been shownto contribute to the regulation of their downstream signaling. β-arrestins interact withthe phosphorylated tail of activated receptors and act as scaffolds for the recruitment ofadaptor proteins and clathrin, that constitute the machinery used for receptorendocytosis. Visual- and β-arrestins have a two-lobe, immunoglobulin-like, β-strandsandwich structure. The recent resolution of the crystal structure of VPS26, one of theretromer subunits, unexpectedly evidenced an arrestin fold in this protein otherwiseunrelated to arrestins. From a functional point of view, VPS26 is involved in theretrograde transport of the mannose 6-P receptor from the endosomes to the trans-Golginetwork. In addition to the group of true arrestins and Vps26, mammalian cells harbor avast repertoire of proteins that are related to arrestins on the basis of their PFAM Nterand Cter arrestin-domains, which are named Arrestin Domain-Containing proteins(ARRDCs). The biological role of ARRDC proteins is still poorly understood. The threesubfamilies have been merged into an arrestin-related protein clan.

This paper provides an overall analysis of arrestin clan proteins. The structures andfunctions of members of the subfamilies are reviewed in mammals and modelorganisms such as Drosophila, Caenorhabditis, Saccharomyces and Dictyostelium.

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Role of Calcium Regulated Kinases: Expressional and Functional Analysis in Abiotic Stress Signaling

Page: 377-425 (49)
Author: Ritika Das, Amita Pandey and Girdhar K. Pandey
DOI: 10.2174/9781608051298113010018

Abstract

Perception of stimuli and activation of a signaling cascade is an intrinsiccharacteristic feature of all living organisms. Till date, several signaling pathways havebeen elucidated that are involved in multiple facets of growth and development of anorganism. Exposure to unfavorable stimuli or stress condition activates differentsignaling cascades in both plants and animal. Being sessile, plants cannot move awayfrom an unfavorable condition, and hence activate the molecular machinery to cope upor adjust against that particular stress condition. In plants, role of calcium as secondmessenger has been studied in detail in both abiotic and biotic stress signaling. Severalcalcium sensor proteins such as calmodulin (CaM), calcium dependent protein kinases(CDPK) and calcinuerin B-like (CBL) protein were discovered to play a crucial role inabiotic stress signaling in plants. Unlike CDPK, CBL and CaM are calcium-bindingproteins, which do not have any protein kinase enzyme activity and interact with atarget protein kinase termed as CBL-interacting protein kinase (CIPK) and CaM kinasesrespectively. Genome sequence analysis of Arabidopsis and rice has led to theidentification of multigene families of these calcium signaling protein kinases.Individual and global gene expression analysis of these protein kinase family membershas been analyzed under several developmental and different abiotic stress conditions.Here, we are making an attempt to overview and emphasize the expressional analysis ofcalcium signaling protein kinases under different abiotic stress and developmentalstages, and linking the expression to possible function for these kinases.

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Multiple Hsp70 Isoforms in the Eukaryotic Cytosol: Evidence for Both Redundant and Specialized Functions

Page: 426-451 (26)
Author: Mehdi Kabani and Céline N. Martineau
DOI: 10.2174/9781608051298113010019

Abstract

Hsp70 molecular chaperones play a variety of functions in every organism,cell type and organelle, and their activities have been implicated in a number of humanpathologies, ranging from cancer to neurodegenerative diseases. The functions,regulations and structure of Hsp70s were intensively studied for about three decades,yet much still remains to be learned about these essential folding enzymes. Genomesequencing efforts revealed that most genomes contain multiple members of the Hsp70family, some of which co-exist in the same cellular compartment. For example, thehuman cytosol and nucleus contain six highly hom*ologous Hsp70 proteins while theyeast Saccharomyces cerevisiae contains four canonical Hsp70s and three fungalspecificribosome-associated and specialized Hsp70s. The reasons and significance ofthe requirement for multiple Hsp70s is still a subject of debate. It has been postulatedfor a long time that these Hsp70 isoforms are functionally redundant and differ only bytheir spatio-temporal expression patterns. However, several studies in yeast and highereukaryotic organisms challenged this widely accepted idea by demonstrating functionalspecificity among Hsp70 isoforms. Another element of complexity is brought about byspecific cofactors, such as Hsp40s or nucleotide exchange factors that modulate theactivity of Hsp70s and their binding to client proteins. Hence, a dynamic network ofchaperone/co-chaperone interactions has evolved in each organism to efficiently takeadvantage of the multiple cellular roles Hsp70s can play. We summarize here ourcurrent knowledge of the functions and regulations of these molecular chaperones, andshed light on the known functional specificities among isoforms.

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Mitochondrial and Nuclear Genes of Mitochondrial Components in Cancer

Page: 452-490 (39)
Author: E. Kirches
DOI: 10.2174/9781608051298113010020

Abstract

Although the observation of aerobic glycolysis of tumor cells by Otto v.Warburg had demonstrated abnormalities of mitochondrial energy metabolism in cancerdecades ago, there was no clear evidence for a functional role of mutant mitochondrialproteins in cancer development until the early years of the 21st century. In the year 2000 amajor breakthrough was achieved by the observation, that several genes coding for subunitsof the respiratory chain (ETC) complex II, succinate dehydrogenase (SDH), are tumorsuppressor genes in heritable paragangliomas, fullfilling Knudson’s classical two-hithypothesis. A functional inactivation of both alleles by germline mutations andchromosomal losses in the tumor tissue was found in the patients. Later, SDH mutationswere also identified in sporadic paragangliomas and pheochromocytomas. Genes of themitochondrial ATP-synthase and of mitochondrial iron homeostasis have been implicatedin cancer development at the level of cell culture and mouse experiments. In contrast to thewell established role of some nuclear SDH genes, a functional impact of the mitochondrialgenome itself (mtDNA) in cancer development remains unclear. Nevertheless, theextremely high frequency of mtDNA mutations in solid tumors raises the question, whetherthis small circular genome might be applicable to early cancer detection. This is ameaningful approach, especially in cancers, which tend to spread tumor cells early intobodily fluids or faeces, which can be screened by non-invasive methods.

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Index

Page: 491-528 (38)
Author: Christian Neri
DOI: 10.2174/9781608051298113010021

Introduction

Genome science or genomics is essential to advancing knowledge in the fields of biology and medicine. Specifically, researchers learn about the molecular biology behind genetic expression in living organisms and related methods of treating human genetic diseases (including gene therapy). Advances in Genome Science is an e-book series which provides a multi-disciplinary view of some of the latest developments in genome research, allowing readers to capture the essentiality and diversity of genomics in contemporary science.

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