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
EZH2 Promotes Expansion of Breast Tumor Initiating Cells through Activation of RAF1-β-Catenin Signaling
Chun Ju Chang,Jer Yen Yang,Weiya Xia,Chun Te Chen,Xiaoming Xie,Chi-Hong Chao,Wendy A. Woodward,Jung Mao Hsu,Gabriel N. Hortobagyi,Mien Chie Hung +9 more
TL;DR: A mechanism in which EZH2 expression-mediated downregulation of DNA damage repair leads to accumulation of recurrent RAF1 gene amplification in BTICs, which activates p-ERK-β-catenin signaling to promote BTIC expansion is identified.
Journal ArticleDOI
RNase H and Multiple RNA Biogenesis Factors Cooperate to Prevent RNA:DNA Hybrids from Generating Genome Instability
Lamia Wahba,Jeremy D. Amon,Douglas Koshland,Douglas Koshland,Douglas Koshland,Milena Vuica-Ross +5 more
TL;DR: In yeast hybrids naturally form at many loci in wild-type cells, but are removed by two evolutionarily conserved RNase H enzymes, indicating that RNA:DNA hybrids are a potent source for changing genome structure.
Journal ArticleDOI
DNA deaminases induce break-associated mutation showers with implication of APOBEC3B and 3A in breast cancer kataegis.
Benjamin Taylor,Serena Nik-Zainal,Yee Ling Wu,Lucy Stebbings,Keiran Raine,Peter J. Campbell,Cristina Rada,Michael R. Stratton,Michael S. Neuberger +8 more
TL;DR: It is shown kataegis can result from AID/APOBEC-catalysed cytidine deamination in the vicinity of DNA breaks, likely through action on single-stranded DNA exposed during resection.
Journal ArticleDOI
DNA confinement in nanochannels: physics and biological applications.
TL;DR: From a physics view these systems are fascinating as they enable probing of single-molecule conformation in environments with dimensions that intersect key physical length-scales in the 1 nm to 100 µm range.
Journal ArticleDOI
Yeast Sen1 helicase protects the genome from transcription-associated instability.
Hannah E. Mischo,Belén Gómez-González,Pawel Grzechnik,Ana G. Rondón,Ana G. Rondón,Wu Wei,Lars M. Steinmetz,Andrés Aguilera,Nick J. Proudfoot +8 more
TL;DR: It is proposed that R loop formation is a frequent event during transcription and a key function of Sen1 is to prevent their accumulation and associated genome instability.
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.