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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Increased Cancer Predisposition in Family Members of Colorectal Cancer Patients Harboring the p.V600E BRAF Mutation: a Population-Based Study
Tyler Wish,Angela Hyde,Patrick S. Parfrey,Jane Green,H. Banfield Younghusband,M Simms,Dan G. Fontaine,Elizabeth Dicks,Susan Stuckless,Steven Gallinger,John R. McLaughlin,Michael O. Woods,Roger C. Green +12 more
TL;DR: The increased incidence of cancer in FDRs of index CRC patients with the p.V600E BRAF mutation may be explained by a genetic predisposition to develop cancer through the serrated pathway of colorectal carcinogenesis.
Journal ArticleDOI
Leveraging DNA damage response signaling to identify yeast genes controlling genome stability.
TL;DR: This work has developed an approach that allows precise, quantitative measurement of genome instability in high-throughput format in the Saccharomyces cerevisiae model system, which takes advantage of the strongly DNA damage-inducible gene RNR3, in conjunction with the reporter synthetic genetic array methodology.
Journal ArticleDOI
Tumor hypoxia and genetic alterations in sporadic cancers
TL;DR: In this review, literature will be presented which supports a third hypothesis, i.e. that hypoxia/re-oxygenation induces genetic instability.
Journal ArticleDOI
Senataxin protects the genome: Implications for neurodegeneration and other abnormalities.
TL;DR: Potentially different roles for senataxin in proliferating and post-mitotic cells are discussed here potentially different roles in transcription termination and RNA splicing are discussed.
Journal ArticleDOI
Regulation of mismatch repair by histone code and posttranslational modifications in eukaryotic cells.
TL;DR: Progress is described in understanding how MMR is carried out in the context of chromatin and how chromatin organization/compaction, epigenetic mechanisms and posttranslational modifications of MMR proteins influence and regulate MMR in eukaryotic cells.
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.