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
Rescuing Stalled or Damaged Replication Forks
TL;DR: Recriming on the leading strand and fork regression are now established as critical for the maintenance and recovery of stalled forks in both prokaryotes and eukaryotes.
Journal ArticleDOI
The evolution of tumour phylogenetics: principles and practice
TL;DR: This work considers this body of work in light of the key computational principles underpinning phylogenetic inference, with the goal of providing practical guidance on the design and analysis of scientifically rigorous tumour phylogeny studies.
Journal ArticleDOI
Cause and consequences of genetic and epigenetic alterations in human cancer.
TL;DR: A model of tumourigenesis is provided that addresses the combined impact of both epigenetic and genetic alterations in cancer cells and considers the associated interactions of genetic and epigenetic processes in tumour onset and progression.
Journal ArticleDOI
Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition
Lynnette R. Ferguson,Helen Chen,Andrew Collins,Marisa Connell,Giovanna Damia,Santanu Dasgupta,Meenakshi Malhotra,Alan K. Meeker,Amedeo Amedei,Amr Amin,Amr Amin,S. Salman Ashraf,Katia Aquilano,Asfar S. Azmi,Dipita Bhakta,Alan Bilsland,Chandra S. Boosani,Sophie Chen,Maria Rosa Ciriolo,Hiromasa Fujii,Gunjan Guha,Dorota Halicka,William G. Helferich,W. Nicol Keith,Sulma I. Mohammed,Elena Niccolai,Xujuan Yang,Kanya Honoki,Virginia R. Parslow,Satya Prakash,Sarallah Rezazadeh,Rodney E. Shackelford,David Sidransky,Phuoc T. Tran,Eddy S. Yang,Christopher A. Maxwell +35 more
TL;DR: Vitamin D and B, selenium, carotenoids, PARP inhibitors, resveratrol, and isothiocyanates are highlighted as priority approaches against genomic instability.
Journal ArticleDOI
Release of Ku and MRN from DNA ends by Mre11 nuclease activity and Ctp1 is required for homologous recombination repair of double-strand breaks.
TL;DR: It is proposed that release of the MRN complex and Ku from DNA ends by Mre11 nuclease activity and Ctp1 is a critical step required to expose ssDNA for RPA localization and ensuing HR repair.
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.