Abstract
Malignant transformation of cells is associated with changes in gene expression. Gross alterations in chromatin organization may be involved in such gene dysregulation, as well as the involvement of specific transcription factors. Specialized genomic DNA segments that exhibit high affinity to the nuclear matrix in vitro have been designated as matrix / scaffold attachment regions (MARs / SARs). MARs are postulated to anchor chromatin onto the nuclear matrix, thereby organizing genomic DNA into topologically distinct loop domains that are important in replication and transcription. In support of this notion, MARs often colocalize or exist in close proximity to regulatory sequences including enhancers. Base unpairing regions (BURs) are typically 100-150 bp regions within MARs, possess an intrinsic propensity to unwind under negative superhelical strain, and are considered to be hallmark of MARs. To investigate a potential mechanism that could lead to significant alterations in gene expression in cancer cells, this review focuses on a group of chromatin-associated proteins that specifically recognize double stranded BURs. Several important proteins have been identified from cancer cells as BUR-binding proteins, including poly (ADP-ribose) polymerase (PARP-1), Ku autoantigen, SAF-A, HMG-I(Y), nucleolin and p53. Many of these proteins are dramatically upregulated in malignancy of the breast. Increase in the amount of these BUR-binding proteins, some of which are known to interact with each other, may not only provide an architectural core but also recruit functional multi-molecular complexes at the base of chromatin loops to affect multiple distant genes. Experimental strategies by which these proteins can be exploited as carcinoma-specific diagnostic markers and as targets for antineoplastic therapy are discussed.
Keywords: chromatin(dis)organization, mars, burs, bur-binding protein, parp-1, saf-a, hmg-1(y),p53
Current Cancer Drug Targets
Title: Chromatin (dis)Organization and Cancer: BUR-binding Proteins as Biomarkers for Cancer
Volume: 2 Issue: 2
Author(s): Sanjeev Galande
Affiliation:
Keywords: chromatin(dis)organization, mars, burs, bur-binding protein, parp-1, saf-a, hmg-1(y),p53
Abstract: Malignant transformation of cells is associated with changes in gene expression. Gross alterations in chromatin organization may be involved in such gene dysregulation, as well as the involvement of specific transcription factors. Specialized genomic DNA segments that exhibit high affinity to the nuclear matrix in vitro have been designated as matrix / scaffold attachment regions (MARs / SARs). MARs are postulated to anchor chromatin onto the nuclear matrix, thereby organizing genomic DNA into topologically distinct loop domains that are important in replication and transcription. In support of this notion, MARs often colocalize or exist in close proximity to regulatory sequences including enhancers. Base unpairing regions (BURs) are typically 100-150 bp regions within MARs, possess an intrinsic propensity to unwind under negative superhelical strain, and are considered to be hallmark of MARs. To investigate a potential mechanism that could lead to significant alterations in gene expression in cancer cells, this review focuses on a group of chromatin-associated proteins that specifically recognize double stranded BURs. Several important proteins have been identified from cancer cells as BUR-binding proteins, including poly (ADP-ribose) polymerase (PARP-1), Ku autoantigen, SAF-A, HMG-I(Y), nucleolin and p53. Many of these proteins are dramatically upregulated in malignancy of the breast. Increase in the amount of these BUR-binding proteins, some of which are known to interact with each other, may not only provide an architectural core but also recruit functional multi-molecular complexes at the base of chromatin loops to affect multiple distant genes. Experimental strategies by which these proteins can be exploited as carcinoma-specific diagnostic markers and as targets for antineoplastic therapy are discussed.
Export Options
About this article
Cite this article as:
Galande Sanjeev, Chromatin (dis)Organization and Cancer: BUR-binding Proteins as Biomarkers for Cancer, Current Cancer Drug Targets 2002; 2 (2) . https://dx.doi.org/10.2174/1568009023333917
DOI https://dx.doi.org/10.2174/1568009023333917 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Related Books

- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
PEGylated Lipid Nanocapsules with Improved Drug Encapsulation and Controlled Release Properties
Current Topics in Medicinal Chemistry Palliative Care for Chest Tumors – Hong Kong, France and Canada
Current Cancer Therapy Reviews Status Quo in Antibody-Drug Conjugates - Can Glyco- Enzymes Solve the Current Challenges?
Protein & Peptide Letters Current Pharmacological Treatment for Male LUTS due to BPH: Dutasteride or Finasteride?
Current Drug Targets Metal-free Reductive Coupling of Biphenyl Tosylhydrazones with Phenols or Benzyl Alcohols
Letters in Organic Chemistry Pharmacokinetic Study of Weekly (Days 1-5) Low-dose S-1 in Patients with Non-Small-Cell Lung Cancer
Reviews on Recent Clinical Trials Role of Iodine, Selenium and Other Micronutrients in Thyroid Function and Disorders
Endocrine, Metabolic & Immune Disorders - Drug Targets Enhanced Risk for Specific Somatic Myeloproliferative Neoplastic Mutations in Patients with Stroke
Current Neurovascular Research 3,4-Dihydroxypyrrolidine as Glycosidase Inhibitor
Current Topics in Medicinal Chemistry Resveratrol and Stroke: from Chemistry to Medicine
Current Neurovascular Research Could Flavonoids Compete with Synthetic Azoles in Diminishing Candida albicans Infections? A Comparative Review Based on In Vitro Studies
Current Medicinal Chemistry Editorial (Thematic Issue: Study and Prediction of Pharmacokinetic Drug-Drug Interactions)
Current Drug Metabolism The Cannabinoid CB2 Receptor as a Target for Inflammation-Dependent Neurodegeneration
Current Neuropharmacology Automated PET Radiotracer Manufacture on the BG75 System and Imaging Validation Studies of [18F]fluoromisonidazole ([18F]FMISO)
Current Radiopharmaceuticals Aim for the Readers! Bromodomains As New Targets Against Chagas’ Disease
Current Medicinal Chemistry Induction of Apoptosis by Nano-Synthesized Complexes of H2L and its Cu(II) Complex in Human Hepatocellular Carcinoma Cells
Anti-Cancer Agents in Medicinal Chemistry Commentary (Research Highlights: WNT-erizing Against Neuropathic Pain)
CNS & Neurological Disorders - Drug Targets The Mevalonate Pathway and Innate Immune Hyper-Responsiveness in the Pathogenesis of COPD and Lung Cancer: Potential for Chemoprevention
Current Molecular Pharmacology Bioinformatic Tools Identify Chromosome-Specific DNA Probes and Facilitate Risk Assessment by Detecting Aneusomies in Extra-embryonic Tissues
Current Genomics Nitrones: A Potential New Alternative as Therapeutic Agents
Current Organic Chemistry