Journal ArticleDOI
The emerging genetic and molecular basis of Fanconi anaemia
Hans Joenje,Ketan J. Patel +1 more
TLDR
The recent cloning of most of the FA-associated genes, and the characterization of their protein products, has provided tantalizing clues as to the molecular basis of this disease.Abstract:
The past few years have witnessed a considerable expansion in our understanding of the pathways that maintain chromosome stability in dividing cells through the identification of genes that are mutated in certain human chromosome instability disorders. Cells that are derived from patients with Fanconi anaemia (FA) show spontaneous chromosomal instability and mutagen hypersensitivity, but FA poses a unique challenge as the nature of the DNA-damage-response pathway thought to be affected by the disease has long been a mystery. However, the recent cloning of most of the FA-associated genes, and the characterization of their protein products, has provided tantalizing clues as to the molecular basis of this disease.read more
Citations
More filters
Journal ArticleDOI
The human disease network
Kwang-Il Goh,Michael E. Cusick,David Valle,Barton Childs,Marc Vidal,Albert-László Barabási,Albert-László Barabási +6 more
TL;DR: This paper found that essential human genes are likely to encode hub proteins and are expressed widely in most tissues, while the vast majority of disease genes are non-essential and show no tendency to encoding hub proteins, and their expression pattern indicates that they are localized in the functional periphery of the network.
Journal Article
human disease network
TL;DR: It is found that essential human genes are likely to encode hub proteins and are expressed widely in most tissues, suggesting that disease genes also would play a central role in the human interactome, and that diseases caused by somatic mutations should not be peripheral.
Journal ArticleDOI
ATM and related protein kinases: safeguarding genome integrity
TL;DR: Understanding ATM's mode of action provides new insights into the association between defective responses to DNA damage and cancer, and brings us closer to resolving the issue of cancer predisposition in some A-T carriers.
Journal ArticleDOI
Biallelic Inactivation of BRCA2 in Fanconi Anemia
Niall G. Howlett,Toshiyasu Taniguchi,Susan B. Olson,Barbara Cox,Quinten Waisfisz,Christine E. M. de Die-Smulders,Nicole Persky,Markus Grompe,Hans Joenje,Gerard Pals,Hideyuki Ikeda,Edward A. Fox,Alan D. D'Andrea +12 more
TL;DR: It is shown that cell lines derived from FA-B and FA-D1 patients have biallelic mutations in BRCA2 and express truncated BRC a2 proteins, which may result in cancer risks similar to those observed in families withBRCA1 or BRCa2 mutations.
Journal ArticleDOI
Molecular views of recombination proteins and their control
TL;DR: The efficient repair of double-strand breaks in DNA is critical for the maintenance of genome stability and cell survival, especially in replicating cells, in which it plays a major role in tumour avoidance.
References
More filters
Book
The Metabolic and Molecular Bases of Inherited Disease
TL;DR: In this paper, the authors present a list of disorders of MITOCHONDRIAL FUNCTION, including the following: DISORDERS OF MIOCHONDRIC FERTILITY XIX, XVI, XIX.
Book
DNA Repair and Mutagenesis
TL;DR: Nucleotide excision repair in mammalian cells: genes and proteins Mismatch repair The SOS response and recombinational repair in prokaryotes Mutagenesis in proKaryote Mutagenisation in eukaryotes Other DNA damage tolerance responses in eUKaryotes.
Journal ArticleDOI
A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage.
Tanya T. Paull,Emmy P. Rogakou,Vikky Yamazaki,Cordula U. Kirchgessner,Martin Gellert,William M. Bonner +5 more
TL;DR: The evidence presented strongly supports a role for the gamma-H2AX and the PI-3 protein kinase family in focus formation at sites of double-strand breaks and suggests the possibility of a change in chromatin structure accompanying double-Strand break repair.
Journal ArticleDOI
XRCC3 promotes homology-directed repair of DNA damage in mammalian cells
TL;DR: It is demonstrated here that error-free homology-directed repair of DNA double-strand breaks is decreased 25-fold in an XR CC3-deficient hamster cell line and can be restored to wild-type levels through XRCC3 expression.
Journal ArticleDOI
RING finger proteins: mediators of ubiquitin ligase activity.
TL;DR: The field of intracellular protein degradation now leaves the era where mediators of substrate-specific ubiquitination were scarce and enters a new and exciting phase where databases provide us with a large number of candidate E3s awaiting characterization.