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
RNA quality control in the nucleus: the Angels' share of RNA.
Odil Porrua,Domenico Libri +1 more
TL;DR: The actors of RNA degradation in the nucleus are described to describe the mechanism of action of these enzymes and examples exist in the literature indicating that many of the principles of RNA quality control described in yeast also apply to other eukaryotes.
Journal ArticleDOI
Dbf4 Is Direct Downstream Target of Ataxia Telangiectasia Mutated (ATM) and Ataxia Telangiectasia and Rad3-related (ATR) Protein to Regulate Intra-S-phase Checkpoint*
Alan Yueh-Luen Lee,Takuya Chiba,Takuya Chiba,Lan N. Truong,An Ning Cheng,An Ning Cheng,Johnny Phong Hoang Do,Michael Jeffrey Cho,Longchuan Chen,Xiaohua Wu +9 more
TL;DR: The studies indicate that DDK is a direct substrate of ATM and ATR to mediate the intra-S-phase checkpoint in mammalian cells to suppress replication initiation and to protect replication forks.
Journal ArticleDOI
The Deubiquitylating Enzyme USP4 Cooperates with CtIP in DNA Double-Strand Break End Resection
Hailong Liu,Haoxing Zhang,Xiaohui Wang,Qingsong Tian,Zhaohua Hu,Changmin Peng,Pei Jiang,Tingting Wang,Wei Guo,Yali Chen,Xinzhi Li,Pumin Zhang,Huadong Pei +12 more
TL;DR: It is found that the deubiquitylating enzyme USP4 directly participates in DSB resection and homologous recombination (HR) and is identified as a key regulator of DNA DSB end resection.
Journal ArticleDOI
Neddylation inhibits CtIP-mediated resection and regulates DNA double strand break repair pathway choice
Sonia Jimeno,María Jesús Fernández-Ávila,Andrés Cruz-García,Andrés Cruz-García,Cristina Cepeda-García,Daniel Gómez-Cabello,Pablo Huertas +6 more
TL;DR: By controlling the length of ssDNA produced during DNA resection, protein neddylation not only affects the choice between NHEJ and homologous recombination but also controls the balance between different recombination subpathways.
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.