Molecular cross-talk among chromosome fragility syndromes
- Jordi Surrallés1,7,
- Stephen P. Jackson2,
- Maria Jasin3,
- Michael B. Kastan4,
- Stephen C. West5, and
- Hans Joenje6
- 1Group of Mutagenesis, Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, 08193-Bellaterra, Barcelona, Spain; 2The Wellcome Trust/Cancer Research UK Institute, University of Cambridge, Cambridge CB2 1QR, UK; 3Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA; 4St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA; 5Cancer Research UK, Clare Hall Laboratories, South Mimms EN6 3LD, UK; 6Free University Medical Center, NL-1081 BT, Amsterdam, The Netherlands
This extract was created in the absence of an abstract.
DNA caretaker genes are defective in several human syndromes known as “chromosomal breakage” or “chromosomal fragility” disorders, which include autosomal recessive diseases such as Fanconi anemia (FA), ataxia telangiectasia (AT), and Nijmegen breakage syndrome (NBS), among others. Dominantly inherited high risk for breast and ovarian cancer is associated with mutations in the BRCA1/BRCA2 genes, whose protein products are also known to be crucial for chromosome stability.
Many of the insights that we have gained into the mechanisms involved in cellular DNA-damage response pathways have come from studies of human cancer susceptibility syndromes that are altered in DNA-damage responses. Basic research on these syndromes is therefore of interest to understand key biological processes that have evolved to maintain a stable genome and to prevent cancer. Research over the last three years has led to the conviction that the pathways involved in many chromosome fragility syndromes converge in a common tumor suppression nuclear network of interactions (Fig. 1). To further characterize how the various proteins involved in these syndromes are interconnected, an International Workshop was organized in the Juan March Centre for International Meetings on Biology (Madrid, Spain, February 2–4, 2004). In this article we summarize the main results presented in this workshop.
Molecular interactions among chromosome fragility syndromes. (A) Each square indicates the molecular nature of the existing interaction between two given syndromes. (B) Diagram representation of the molecular cross-talk. Each line connects syndromes with known interaction at the molecular level as detailed in A.
The first session was fully dedicated to FA, which is characterized at the cellular level by chromatid-type breakage of metaphase chromosomes, in particular after exposure to cross-linking agents such as mitomycin C (MMC). Hans Joenje (Amsterdam, The Netherlands) presented a comprehensive up-to-date summary of the latest discoveries relating to genetics and molecular biology of this …
