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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Deficiency in Mammalian Histone H2B Ubiquitin Ligase Bre1 (Rnf20/Rnf40) Leads to Replication Stress and Chromosomal Instability
Sophia B. Chernikova,Olga V. Razorenova,John P. Higgins,Brock J. Sishc,Monica Nicolau,Jennifer A. Dorth,Diana A. Chernikova,Shirley Kwok,James D. Brooks,Susan M. Bailey,John C. Game,J. Martin Brown +11 more
TL;DR: It is proposed that genomic instability triggered by Bre1 deficiency may be an important early step that precedes acquisition of an invasive phenotype, as decreased levels of BRE1A/B and dimethylated H3K79 in testicular seminoma and in the premalignant lesion in situ carcinoma are found.
Journal ArticleDOI
Origins and activity of the Mediator complex
TL;DR: A brief overview of the evolutionary origins of Mediator, its subunit composition, and its remarkably diverse collection of activities in Pol II transcription is provided.
Journal ArticleDOI
RecA maintains the integrity of chloroplast DNA molecules in Arabidopsis.
TL;DR: The process by which damaged DNA is repaired in bacteria has been retained in their endosymbiotic descendent, the chloroplast, as seen in cprecA mutants.
Journal ArticleDOI
Impediments to replication fork movement: stabilisation, reactivation and genome instability
TL;DR: What is known about potential barriers to replication fork progression, how these are tolerated and their impact on genome instability are reviewed.
Journal ArticleDOI
A Synthetic Lethal Screen Identifies DNA Repair Pathways that Sensitize Cancer Cells to Combined ATR Inhibition and Cisplatin Treatments
Kareem N. Mohni,Petria S. Thompson,Jessica W. Luzwick,Gloria G. Glick,Christopher S Pendleton,Brian D. Lehmann,Jennifer A. Pietenpol,David Cortez +7 more
TL;DR: The first synthetic lethality screen with a combination treatment of an ATR inhibitor (ATRi) and cisplatin and it is reported that ATRi strongly synergizes with PARP inhibition, even in homologous recombination-proficient backgrounds.
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.