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
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Shelterin and the replisome: at the intersection of telomere repair and replication
Alessandro Cicconi,Sandy Chang +1 more
TL;DR: The most recent discoveries documenting the mechanisms by which shelterin represses DNA repair pathways at telomeres while assisting its replication highlight a novel connection between telomere maintenance and repair.
Journal ArticleDOI
Gene amplification system based on double rolling-circle replication as a model for oncogene-type amplification
TL;DR: A gene amplification system in yeast and mammalian cells that is based on double rolling-circle replication (DRCR) that shows distinctive features seen in amplification of oncogenes and drug-resistance genes, and can improve amplification systems used for making pharmaceutical proteins in mammalian cells.
Journal ArticleDOI
Short inverted repeats contribute to localized mutability in human somatic cells.
Xueqing Zou,Sandro Morganella,Dominik Glodzik,Helen Davies,Yilin Li,Michael R. Stratton,Serena Nik-Zainal,Serena Nik-Zainal +7 more
TL;DR: It is shown that SIRs confer an increase in localized mutability in breast cancer, which is domain-dependent with the greatest mutability observed within spacer sequences (∼1.35-fold above background).
Journal ArticleDOI
Application of SNP microarrays to the genome-wide analysis of chromosomal instability in premalignant airway lesions.
Ichiro Nakachi,Jessica L. Rice,Christopher D. Coldren,Michael G. Edwards,Robert Stearman,Steven C. Glidewell,Marileila Varella-Garcia,Wilbur A. Franklin,Robert L. Keith,Marina T. Lewis,Bifeng Gao,Daniel T. Merrick,York E. Miller,Mark W. Geraci +13 more
TL;DR: SNP arrays combined with delta-θ analysis can detect SCAs in heterogeneous clinical sample and expand the ability to assess genomic instability in the airway epithelium as a biomarker of lung cancer risk.
Journal ArticleDOI
Underappreciated Roles of DNA Polymerase δ in Replication Stress Survival.
TL;DR: In this paper, structural analysis of Fe-S centers in replication proteins and insights into the structure and function of DNA polymerase δ (DNA Pol δ) subunits have shed light on the key role played by this polymerase at replication forks under stress.
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.