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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High levels of transcription stimulate transversions at GC base pairs in yeast.
Matthew P. Alexander,Kaitlyn J. Begins,William C. Crall,Margaret P. Holmes,Malcolm J. Lippert +4 more
TL;DR: Results indicate that transcription‐dependent G→T and G→C transversions in yeast differ mechanistically from equivalent events in E. coli reported by others, and represent a novel type of transcription‐associated mutagenesis in normal cells with potentially important implications for evolution and genetic disease.
Journal ArticleDOI
Efficient Replication of the Plastid Genome Requires an Organellar Thymidine Kinase.
Monique Le Ret,Susan Belcher,Stéfanie Graindorge,Clémentine Wallet,Sandrine Koechler,Mathieu Erhardt,Rosalind Williams-Carrier,Alice Barkan,José M. Gualberto +8 more
TL;DR: These and other results suggest that the loss of normal cpDNA replication elicits the mobilization of new replication origins around the rpoB (beta subunit of plastid-encoded RNA polymerase) transcription unit and imply that increased transcription at rPOB is associated with the initiation of cp DNA replication.
Journal ArticleDOI
EGFP-Rhm51 foci enable the visualization and enumeration of DNA double-strand breaks in Magnaporthe oryzae
TL;DR: EGFP-Rhm51 foci were observed at all stages of the asexual cycle including when invasive hyphae formed in an intact rice leaf sheath, demonstrating that M. oryzae undergoes DSBs during vegetative and parasitic growth.
Journal ArticleDOI
GTPases, genome, actin: A hidden story in DNA damage response and repair mechanisms.
Yuli Thamires Magalhães,Jessica Oliveira Farias,Luiz Eduardo Virgilio Silva,Fabio Luis Forti +3 more
TL;DR: In this article, the authors provide a contextualized review of the interplay between Rho GTPase signaling pathways and the DNA damage response and DNA repair signaling components, and highlight the direct and indirect targets, some of which still lack experimental validation data, likely associated with RhoGTPase activation that provides compelling evidence for further investigation in DNA damageassociated events and with potential therapeutic applications in translational medicine.
Journal ArticleDOI
In vivo importance of homologous recombination DNA repair for mouse neural stem and progenitor cells.
Laure Rousseau,Olivier Etienne,Telma Roque,Chantal Desmaze,Céline Haton,Marc-André Mouthon,Jacqueline Bernardino-Sgherri,Jeroen Essers,Roland Kanaar,François D. Boussin +9 more
TL;DR: The data support the existence of RAD54-dependent and -independent homologous recombination pathways and the importance of Rad54 for radiation response was linked to the cell cycle phase at the time of irradiation and not to the differentiation state.
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.