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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Molecular mechanisms by which in vivo exposure to exogenous chemical genotoxic agents can lead to micronucleus formation in lymphocytes in vivo and ex vivo in humans
Michael Fenech,Siegfried Knasmueller,Claudia Bolognesi,Stefano Bonassi,Nina Holland,Lucia Migliore,Fabrizio Palitti,Adayapalam T. Natarajan,Micheline Kirsch-Volders +8 more
TL;DR: Current knowledge on the molecular mechanisms by which in vivo exposure to exogenous chemical genotoxins in humans induces micronuclei (MNi) and other nuclear anomalies in lymphocytes in vivo and ex vivo after nuclear division in vitro is summarized.
Journal ArticleDOI
Stabilization and targeting of INO80 to replication forks by BAP1 during normal DNA synthesis
TL;DR: It is found that Ino80, which encodes the catalytic ATPase of INO80, is essential for mouse embryonic DNA replication and development and uncovered a mechanism by which this remodeler is targeted to replication forks, suggesting a molecular basis for the tumour-suppressing function of BAP1.
Journal ArticleDOI
Recovery of arrested replication forks by homologous recombination is error-prone.
Ismail Iraqui,Ismail Iraqui,Yasmina Chekkal,Yasmina Chekkal,Nada Jmari,Nada Jmari,Violena Pietrobon,Violena Pietrobon,Karine Fréon,Karine Fréon,Audrey Costes,Audrey Costes,Sarah Lambert,Sarah Lambert +13 more
TL;DR: The data establish that collapsed forks, but not stalled forks, recovered by homologous recombination are prone to replication slippage, and it is proposed that deletions/insertions, mediated by micro-homology, leading to copy number variations during replication stress may arise by progression of error-prone replication forks restarted by homologies recombination.
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Deregulated telomere transcription causes replication-dependent telomere shortening and promotes cellular senescence
TL;DR: It is shown that in order for telomere loss to occur, transcription must pass through the telomeres tract itself producing a TERRA molecule, which suggests that telomerase and homology directed repair must be tightly controlled to prevent telitere loss and early onset senescence.
Journal ArticleDOI
The conflict between DNA replication and transcription
TL;DR: This review summarizes what is currently known about how collisions between replisomes and transcription complexes are minimized and the mechanisms that help to resolve such collisions when they do occur.
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.