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 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- 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
-
Synthesis and Anti Lung Cancer Activity of 3-Arylspiro[oxirane-2,3'- thiochroman]-4'-one Derivatives
Letters in Organic Chemistry Small Molecules Targeting Mutant P53: A Promising Approach for Cancer Treatment
Current Medicinal Chemistry Synthesis of Aryl-Substituted Naphthalenoids as Potent Topoisomerase Inhibitors
Medicinal Chemistry Mitogen-activated Protein Kinase Kinase 6-fusion Protein (MAP2K6-FP) Potentiates the Anti-tumor effects of Paclitaxel in Ovarian Cancer
Anti-Cancer Agents in Medicinal Chemistry Recent Applications of Triazolopyrimidine-Based Bioactive Compounds in Medicinal and Agrochemical Chemistry
Mini-Reviews in Medicinal Chemistry Acknowledgements to Reviewers
Current Biomarkers (Discontinued) Acknowledgements to the Reviewers
Current Cancer Drug Targets subject Index To Volume 2
Current Cancer Drug Targets The Influence of Different Spacers on Biological Profile of Peptide Radiopharmaceuticals for Diagnosis and Therapy of Human Cancers
Anti-Cancer Agents in Medicinal Chemistry Thermal Assisted In Vivo Gene Electrotransfer
Current Gene Therapy Carbonic Anhydrases An Overview
Current Pharmaceutical Design Epigenetically - Targeted Therapies for the Treatment of Hematological Malignancies
Current Medicinal Chemistry “Bedside-to-Bench” Behavioral Outcomes in Animal Models of Pain: Beyond the Evaluation of Reflexes
Current Neuropharmacology Epigenetic Targets and their Inhibitors in Cancer Therapy
Current Topics in Medicinal Chemistry New Therapeutic Strategies for Castration-Resistant Prostate Cancer
Recent Patents on Anti-Cancer Drug Discovery Selectively Replicating Adenoviruses for Oncolytic Therapy
Current Cancer Drug Targets Association of Folate Level in Blood with the Risk of Schizophrenia
Combinatorial Chemistry & High Throughput Screening Molecular Dynamics and Structural Studies of the Ets Domain-DNA Complexes
Current Bioinformatics Drug Discovery and Protein Tyrosine Phosphatases
Current Medicinal Chemistry Synthetic Curcumin Analog UBS109 Inhibits the Growth of Head and Neck Squamous Cell Carcinoma Xenografts
Current Cancer Drug Targets