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
Loss of DNA Replication Control Is a Potent Inducer of Gene Amplification
TL;DR: It is suggested that re-replication may be a contributor to gene copy number changes, which are important in fields such as cancer biology, evolution, and human genetics.
Journal ArticleDOI
DNA replication as a target of the DNA damage checkpoint.
TL;DR: The focus of this review is how DNA replication is regulated by the checkpoint response in the presence of DNA damage and fork stalling agents.
Journal ArticleDOI
Human Timeless and Tipin stabilize replication forks and facilitate sister-chromatid cohesion
TL;DR: Timeless-Tipin functions as a replication fork stabilizer that couples DNA replication with sister chromatid cohesion established at replication forks, suggesting that it is required for replication fork maintenance under stress.
Journal ArticleDOI
Regulatory networks integrating cell cycle control with DNA damage checkpoints and double-strand break repair.
Petra Langerak,Paul Russell +1 more
TL;DR: Recent findings are reviewed and insight is provided on how proteins that regulate cell cycle progression affect DSB repair, and, conversely, howprotein that repair DSBs affectcell cycle progression.
Journal ArticleDOI
Senataxin Mutation Reveals How R-Loops Promote Transcription by Blocking DNA Methylation at Gene Promoters
Christopher Grunseich,Isabel X. Wang,Jason A. Watts,Joshua T. Burdick,Robert D. Guber,Zhengwei Zhu,Alan Bruzel,Tyler Lanman,Ke-lian Chen,Alice B. Schindler,Nancy A. Edwards,Abhik Ray-Chaudhury,Jianhua Yao,Tanya J. Lehky,Grzegorz Piszczek,Barbara J. Crain,Kenneth H. Fischbeck,Vivian G. Cheung,Vivian G. Cheung +18 more
TL;DR: Results show that nucleic acid structures, in addition to sequences, influence the binding and activity of regulatory proteins in genome-wide R-loops.
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.