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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Journal ArticleDOI
Chromatin and alternative splicing.
Mariano Alló,Ignacio E. Schor,Manuel Javier Muñoz,M. de la Mata,Eneritz Agirre,Juan Valcárcel,Eduardo Eyras,Alberto R. Kornblihtt +7 more
TL;DR: The evidence supporting the first proposal of chromatin affecting alternative splicing, performed 20 years ago, is discussed, including genome-wide evidence that nucleosomes are preferentially positioned in exons, and two recent reports from laboratories that add new evidence to this field.
Journal ArticleDOI
Splicing events in the control of genome integrity: role of SLU7 and truncated SRSF3 proteins.
Maddalen Jimenez,Raquel Urtasun,M.R. Elizalde,María Azkona,M. Ujue Latasa,Iker Uriarte,Iker Uriarte,María Arechederra,Diego Alignani,Marina Bárcena-Varela,Gloria Alvarez-Sola,Gloria Alvarez-Sola,Leticia Colyn,Eva Santamaría,Eva Santamaría,Bruno Sangro,C.M. Rodriguez-Ortigosa,C.M. Rodriguez-Ortigosa,Maite G. Fernandez-Barrena,Maite G. Fernandez-Barrena,Matías A. Avila,Matías A. Avila,Carmen Berasain,Carmen Berasain +23 more
TL;DR: A molecular pathway through which SLU7 keeps in check the generation of truncated forms of the splicing factor SRSF3 (SRp20) (SRSF 3-TR) is defined, demonstrating a conserved and fundamental role ofSLU7 in the preservation of genome integrity.
Journal ArticleDOI
TPX2/Aurora kinase A signaling as a potential therapeutic target in genomically unstable cancer cells
Stephanie E van Gijn,Elles Wierenga,Nathalie van den Tempel,Yannick P Kok,Anne Margriet Heijink,Diana C.J. Spierings,Floris Foijer,Marcel A. T. M. van Vugt,Rudolf S N Fehrmann +8 more
TL;DR: The findings reveal that BRCA2-deficient cancer cells show enhanced sensitivity to inactivation of TPX2 or its partner Aurora-A, which points at an actionable dependency of genomically unstable cancers.
Journal ArticleDOI
Transcription and replication: breaking the rules of the road causes genomic instability.
TL;DR: Replication and transcription machineries progress at high speed on the same DNA template, which inevitably causes traffic accidents and induces genomic instability by blocking fork progression and could be implicated in the development of cancer.
Journal ArticleDOI
A core hSSB1–INTS complex participates in the DNA damage response
Feng Zhang,Teng Ma,Xiaochun Yu +2 more
TL;DR: Using protein affinity purification, it is identified integrator complex subunit 6 (INTS6) as a major subunit of the core hSSB1 complex, which regulates the accumulation of RAD51 and BRCA1 at DNA damage sites and the correlated homologous recombination.
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.