Journal ArticleDOI
Genome instability: a mechanistic view of its causes and consequences
TLDR
The causes and consequences of instability are reviewed with the aim of providing a mechanistic perspective on the origin of genomic instability.Abstract:
Genomic instability in the form of mutations and chromosome rearrangements is usually associated with pathological disorders, and yet it is also crucial for evolution. Two types of elements have a key role in instability leading to rearrangements: those that act in trans to prevent instability--among them are replication, repair and S-phase checkpoint factors--and those that act in cis--chromosomal hotspots of instability such as fragile sites and highly transcribed DNA sequences. Taking these elements as a guide, we review the causes and consequences of instability with the aim of providing a mechanistic perspective on the origin of genomic instability.read more
Citations
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Journal ArticleDOI
Radiation-induced chromosomal instability under constrained growth of irradiated cells.
TL;DR: It was hypothesized that the mechanisms of generation of chromosomal breaks in the progeny of irradiated cells involve a cycle of chro mosome breakages and fusions, increased level of reactive oxygen species (ROS), altered DNA repli cation or replicative stress, activation of fragile sites, and telomere dysfunction under the influence of radi ation.
Journal ArticleDOI
Introductory comments on special section-genomic microduplications: When adding may equal subtracting.
TL;DR: The clinical implementation of array‐based comparative genomic hybridization (aCGH) has allowed detection of copy number variations (CNVs) from megabases in size to those involving only a single exon, but the interpretation of CNVs whose clinical significance can be elusive.
Journal ArticleDOI
How heterogeneity drives tumour growth: a computational study.
TL;DR: It is observed that even a mild heterogeneity in the proliferation rates of different cell subpopulations leads to a much faster overall tumour growth when compared to a homogeneous tumour.
Dissertation
Linkage mapping and genetic analysis of Trypanosoma brucei
TL;DR: The construction of a separate genetic map for the sub-species responsible for > 90% of human African trypanosomiasis infections, T.b.brucei, is described, which can be utilised to find the location within the genome of genes responsible for phenotypic traits in this clinically important sub- species.
Journal ArticleDOI
Chromosome instability and tumor lethality suppression in carcinogenesis.
TL;DR: A tumor lethality suppression concept is discussed based on the studies of yeast genetic interactions and transgenic mice to elucidate the role of CIN in tumorigenesis, the relationship between CIN and somatic gene mutations, and the design of anticancer drug development.
References
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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
Instability and decay of the primary structure of DNA
TL;DR: The spontaneous decay of DNA is likely to be a major factor in mutagenesis, carcinogenesis and ageing, and also sets limits for the recovery of DNA fragments from fossils.
Journal ArticleDOI
DNA Double-stranded Breaks Induce Histone H2AX Phosphorylation on Serine 139
TL;DR: In this paper, a histone H2AX species that has been phosphorylated specifically at serine 139 was found to be a major component of DNA double-stranded break.
Journal ArticleDOI
ATM Phosphorylates Histone H2AX in Response to DNA Double-strand Breaks
TL;DR: The results clearly establish ATM as the major kinase involved in the phosphorylation of H2AX and suggest that ATM is one of the earliest kinases to be activated in the cellular response to double-strand breaks.
Journal ArticleDOI
Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions
Vassilis G. Gorgoulis,Leandros-Vassilios F. Vassiliou,Panagiotis Karakaidos,Panayotis Zacharatos,Athanassios Kotsinas,Triantafillos Liloglou,Monica Venere,Richard A. DiTullio,Nikolaos G. Kastrinakis,Brynn Levy,Dimitris Kletsas,Akihiro Yoneta,Meenhard Herlyn,Christos Kittas,Thanos D. Halazonetis,Thanos D. Halazonetis +15 more
TL;DR: A panel of human lung hyperplasias, all of which retained wild-type p53 genes and had no signs of gross chromosomal instability, and found signs of a DNA damage response, including histone H2AX and Chk2 phosphorylation, p53 accumulation, focal staining of p53 binding protein 1 (53BP1) and apoptosis as discussed by the authors.