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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CD133+ Glioblastoma Stem-like Cells are Radiosensitive with a Defective DNA Damage Response Compared with Established Cell Lines
TL;DR: The data indicate that the mechanisms through which CD133+ TSCs respond to radiation are significantly different from those of the traditional glioblastoma in vitro model, established glioma cell lines, likely to be of consequence in the development and testing of radiosensitizing agents.
Journal ArticleDOI
DNA template strand sequencing of single-cells maps genomic rearrangements at high resolution
Ester Falconer,Mark Hills,Ulrike Naumann,Steven S.S. Poon,Elizabeth A. Chavez,Ashley D. Sanders,Yongjun Zhao,Martin Hirst,Peter M. Lansdorp +8 more
TL;DR: Strand-seq was developed to independently sequence parental DNA template strands from single cells, making it possible to map SCEs at orders-of-magnitude greater resolution than was previously possible.
Journal ArticleDOI
Chromosomal instability (CIN): what it is and why it is crucial to cancer evolution
Henry H.Q. Heng,Steven W. Bremer,Joshua B. Stevens,Steven D. Horne,Guo Liu,Batoul Y. Abdallah,Karen J. Ye,Christine J. Ye +7 more
TL;DR: This review discusses multiple aspects of CIN including its definitions, methods of measuring, and some common misconceptions and applies the genome-based evolutionary theory to propose a general mechanism for CIN to unify the diverse molecular causes.
Journal ArticleDOI
RECQL5 Controls Transcript Elongation and Suppresses Genome Instability Associated with Transcription Stress
Marco Saponaro,Theodoros Kantidakis,Richard Mitter,Gavin Kelly,Mark Heron,Hannah Williams,Johannes Söding,Aengus Stewart,Jesper Q. Svejstrup +8 more
TL;DR: The chromosomal breakpoints overlap with areas of elevated transcription stress, suggesting that RECQL5 suppresses such stress and its detrimental effects, and thereby prevents genome instability in the transcribed region of genes.
Journal ArticleDOI
Rep Provides a Second Motor at the Replisome to Promote Duplication of Protein-Bound DNA
Colin P. Guy,John Atkinson,Milind Kumar Gupta,Akeel A. Mahdi,Emma J. Gwynn,Christian J. Rudolph,Peter B. Moon,Ingeborg van Knippenberg,Chris J. Cadman,Mark S. Dillingham,Robert G. Lloyd,Peter McGlynn +11 more
TL;DR: Rep and UvrD each promote movement of E. coli replisomes blocked by nucleoprotein complexes in vitro and provide two contrasting solutions as to how organisms may promote replication of protein-bound DNA.
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.