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
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DissertationDOI
Role of RAGE in melanoma development, growth, and progression
TL;DR: The study provided evidence that the observed benefits of a high RAGE expression on melanoma cells, including sustained proliferation, deregulation of cellular energetics, and prolonged survival, also come along with negative effects such as higher vulnerability to exogenous genotoxic insults.
Journal ArticleDOI
Role of FEN1 S187 phosphorylation in counteracting oxygen-induced stress and regulating postnatal heart development.
Lina Zhou,Huifang Dai,Jian Wu,Mian Zhou,Hua Yuan,Juan Du,Lu Yang,Xiwei Wu,Hong Xu,Yuejin Hua,Jian Xu,Li Zheng,Binghui Shen +12 more
TL;DR: An in vivo role is reported for FEN1 phosphorylation in counteracting oxygen‐induced stress and regulating postnatal heart development and maintaining proper cell cycle progression.
Journal ArticleDOI
CtIP-Specific Roles during Cell Reprogramming Have Long-Term Consequences in the Survival and Fitness of Induced Pluripotent Stem Cells.
TL;DR: It is revealed thatReprogramming is associated with high levels of DNA end resection, a critical step in homologous recombination, and it is demonstrated that reprogramming in a resection-defective environment has long-term consequences on stem cell self-renewal and differentiation.
Journal ArticleDOI
Use of RecA fusion proteins to induce genomic modifications in zebrafish
Hsin-kai Liao,Jeffrey J. Essner +1 more
TL;DR: The data support a model whereby NLS-RecA-Gal4 DNA filaments bind to complementary target sites on chromatin and stall DNA replication forks, resulting in a DNA DSB, and lesions in ∼9% of the F0 zebrafish are transmitted to subsequent generations as large chromosomal deletions.
Journal ArticleDOI
Micronucleus frequency in peripheral blood lymphocytes and frailty status in elderly. A lack of association with clinical features
Vanessa Valdiglesias,Stefano Bonassi,Valentina Dell'Armi,Silvana Settanni,Michela Celi,Simona Mastropaolo,Manuela Antocicco,Massimo Fini,Graziano Onder +8 more
TL;DR: No association between MN frequency and frailty status was found under the specific conditions tested in this study, and the inclusion of MN frequency in the Fried's frailty scale minimally improved the classification of study subjects according to the multidimensional prognostic index (MPI).
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.