Abstract
BRCA1, a breast and ovarian tumor suppressor, maintains genome stability through its functions in DNA repair, cell-cycle checkpoints, heterochromatin formation and centrosome amplification. BRCA1 interacts with BARD1 to constitute a RING heterodimer-type E3 ubiquitin ligase. BRCA1-associated protein 1 (BAP1) is a deubiquitinating enzyme that also regulates similar cellular events, including cell-cycle control, transcription, chromatin modification and DNA damage response. Germline mutations in BRCA1 predispose individuals to breast, ovarian, fallopian tube, peritoneal, pancreatic and prostate cancers, whereas BAP1 mutations combined with certain types of DNA damage provoke malignant mesothelioma, uveal and cutaneous melanoma, lung adenocarcinoma and renal cell carcinoma. Although BAP1 was initially discovered as a BRCA1-associated protein, recent mass-spectrometric screens of BAP1 interactors failed to detect BRCA1, raising questions about their presumed endogenous interaction. However, in addition to physical interaction, new evidence indicates a functional correlation between the two proteins. This review summarizes BAP1 function in histone modification and the DNA damage response, focusing on BAP1’s relevance to BRCA1 function. An understanding of the cooperative functions between BRCA1 and BAP1 may uncover opportunities for new drug targets in a variety of related cancers.
Keywords: BRCA1, BAP1, DNA damage response, Histone modification, Polycomb.
Current Cancer Drug Targets
Title:Functional Link between BRCA1 and BAP1 through Histone H2A, Heterochromatin and DNA Damage Response
Volume: 16 Issue: 2
Author(s): Takayo Fukuda, Tomoko Tsuruga, Takako Kuroda, Hiroyuki Nishikawa and Tomohiko Ohta
Affiliation:
Keywords: BRCA1, BAP1, DNA damage response, Histone modification, Polycomb.
Abstract: BRCA1, a breast and ovarian tumor suppressor, maintains genome stability through its functions in DNA repair, cell-cycle checkpoints, heterochromatin formation and centrosome amplification. BRCA1 interacts with BARD1 to constitute a RING heterodimer-type E3 ubiquitin ligase. BRCA1-associated protein 1 (BAP1) is a deubiquitinating enzyme that also regulates similar cellular events, including cell-cycle control, transcription, chromatin modification and DNA damage response. Germline mutations in BRCA1 predispose individuals to breast, ovarian, fallopian tube, peritoneal, pancreatic and prostate cancers, whereas BAP1 mutations combined with certain types of DNA damage provoke malignant mesothelioma, uveal and cutaneous melanoma, lung adenocarcinoma and renal cell carcinoma. Although BAP1 was initially discovered as a BRCA1-associated protein, recent mass-spectrometric screens of BAP1 interactors failed to detect BRCA1, raising questions about their presumed endogenous interaction. However, in addition to physical interaction, new evidence indicates a functional correlation between the two proteins. This review summarizes BAP1 function in histone modification and the DNA damage response, focusing on BAP1’s relevance to BRCA1 function. An understanding of the cooperative functions between BRCA1 and BAP1 may uncover opportunities for new drug targets in a variety of related cancers.
Export Options
About this article
Cite this article as:
Fukuda Takayo, Tsuruga Tomoko, Kuroda Takako, Nishikawa Hiroyuki and Ohta Tomohiko, Functional Link between BRCA1 and BAP1 through Histone H2A, Heterochromatin and DNA Damage Response, Current Cancer Drug Targets 2016; 16 (2) . https://dx.doi.org/10.2174/1568009615666151030102427
DOI https://dx.doi.org/10.2174/1568009615666151030102427 |
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
-
Biotransformation of Endocrine Disrupting Compounds by Selected Phase I and Phase II Enzymes – Formation of Estrogenic and Chemically Reactive Metabolites by Cytochromes P450 and Sulfotransferases
Current Medicinal Chemistry From Bacteria to Antineoplastic: Epothilones A Successful History
Anti-Cancer Agents in Medicinal Chemistry Sentinel Lymph Node Mapping in Early Stage Endometrial Cancer Patients in Low-Resource Settings
Current Women`s Health Reviews Tubulin Maytansine Site Binding Ligands and their Applications as MTAs and ADCs for Cancer Therapy
Current Medicinal Chemistry How Do Microbubbles and Ultrasound Interact? Basic Physical, Dynamic and Engineering Principles
Current Pharmaceutical Design Mechanisms of Tubulin Binding Ligands to Target Cancer Cells: Updates on their Therapeutic Potential and Clinical Trials
Current Cancer Drug Targets The Role of Maternal Serum Biomarkers in the Early Diagnosis of Ectopic Pregnancy
Current Chemical Biology Transmission Electron Microscopy as Key Technique for the Characterization of Telocytes
Current Stem Cell Research & Therapy Recent Progress: Gynecologic Oncology Group Trials in Uterine Corpus Tumors
Reviews on Recent Clinical Trials Development of Genetic Testing for Breast, Ovarian and Colorectal Cancer Predisposition: A Step Closer to Targeted Cancer Prevention
Current Drug Targets Pertinence of Apoptosis Markers for the Improvement of In Vitro Fertilization (IVF)
Current Medicinal Chemistry Review of Dose-intense Platinum and/or Paclitaxel Containing Chemotherapy in Advanced and Recurrent Epithelial Ovarian Cancer
Current Pharmaceutical Design Nanocarriers Based Anticancer Drugs: Current Scenario and Future Perceptions
Current Drug Targets Therapeutic Peptide Mimetics Looking for a Turn to Block Aberrant Players of Malignancy
Current Cancer Therapy Reviews Trebananib (AMG 386): A Non-VEGF Antiangiogenesis Option in Women with Ovarian Cancer
Current Angiogenesis (Discontinued) Angiotensin-(1-7): A Peptide Hormone with Anti-Cancer Activity
Current Medicinal Chemistry Microtubule Targeting Agents: A Benchmark in Cancer Therapy
Current Drug Therapy Targeting Post-Ejaculation Sperm for Value-Added Contraception
Current Molecular Pharmacology Surgical Strategies for Fertility Preservation in Women with Cancer
Current Women`s Health Reviews Recent Patents for Homologous Recombination Deficiency Assays Among Women with Ovarian Cancer
Recent Patents on Biotechnology