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
More filters
Journal ArticleDOI
Acute inactivation of the replicative helicase in human cells triggers MCM8–9-dependent DNA synthesis
Toyoaki Natsume,Kohei Nishimura,Sheroy Minocherhomji,Rahul Bhowmick,Ian D. Hickson,Masato T. Kanemaki +5 more
TL;DR: It is proposed that stalled replication forks can be restarted in S phase via homologous recombination using MCM8-9 as an alternative replicative helicase.
Journal ArticleDOI
Cellular interactions constrain tumor growth.
Jeffrey West,Paul K. Newton +1 more
TL;DR: A statistical mechanics approach is developed that focuses on the total number of possible states each cell can occupy and shows how different assumptions on correlations of these states give rise to the many different macroscopic tumor growth laws used in the literature.
Journal ArticleDOI
Chromoanagenesis: cataclysms behind complex chromosomal rearrangements.
TL;DR: The concept of chromanagenesis has provided new insight into the aetiology of complex structural rearrangements, the connection between defective cell cycle progression and genomic instability, and the complexity of cancer evolution.
Journal ArticleDOI
Dna2 is a structure-specific nuclease, with affinity for 5′-flap intermediates
TL;DR: Using DNA binding competition assays, it is found that Dna2 has substrate structure specificity and recognized and bound both the single-stranded flap and portions of the duplex region immediately downstream of the flap.
Journal ArticleDOI
PriC-mediated DNA replication restart requires PriC complex formation with the single-stranded DNA-binding protein.
Sarah R. Wessel,Aimee H. Marceau,Shawn C. Massoni,Ruobo Zhou,Taekjip Ha,Steven J. Sandler,James L. Keck +6 more
TL;DR: A direct interaction is defined between PriC, a key Escherichia coli DNA replication restart protein, and the single-stranded DNA-binding protein (SSB), a protein that is ubiquitously associated with DNA replication forks to create a DNA structure that is competent for DnaB loading.
References
More filters
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.