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
Cell cycle, CDKs and cancer: a changing paradigm
TL;DR: Genetic evidence suggests that tumour cells may also require specific interphase CDKs for proliferation, and selective CDK inhibition may provide therapeutic benefit against certain human neoplasias.
Journal ArticleDOI
cGAS surveillance of micronuclei links genome instability to innate immunity
Karen J. Mackenzie,Paula Carroll,Carol Anne Martin,Olga Murina,Adeline Fluteau,Daniel J. Simpson,Nelly Olova,Hannah Sutcliffe,Jacqueline K. Rainger,Andrea Leitch,Ruby T. Osborn,Ann P. Wheeler,Marcin Nowotny,Nick Gilbert,Tamir Chandra,Martin A M Reijns,Andrew P. Jackson +16 more
TL;DR: It is reported that cGAS localizes to micronuclei arising from genome instability in a mouse model of monogenic autoinflammation, after exogenous DNA damage and spontaneously in human cancer cells, and it is established that interferon-stimulated gene expression is induced inmicronucleated cells, concluding that micronsuclei represent an important source of immunostimulatory DNA.
Journal ArticleDOI
Living on a break: cellular senescence as a DNA-damage response.
TL;DR: The diverse mechanisms that lead to DNA-damage generation and the activation of DNA- damage-response signalling pathways are discussed, together with the evidence for their contribution to the establishment and maintenance of cellular senescence in the context of organismal ageing and cancer development.
Journal ArticleDOI
R Loops: From Transcription Byproducts to Threats to Genome Stability
TL;DR: The factors and cellular processes that control R loop formation and the mechanisms by which R loops may influence gene expression and the integrity of the genome are discussed.
Journal ArticleDOI
Maintaining genome stability at the replication fork.
Dana Branzei,Marco Foiani +1 more
TL;DR: These mechanisms ensure that the local DNA damage response, which enables replication fork progression and DNA repair in S phase, is coupled with cell cycle transitions.
References
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Journal ArticleDOI
The Transcription Elongation Complex Directs Activation-Induced Cytidine Deaminase-Mediated DNA Deamination
TL;DR: It is shown that AID binds DNA exposed by the transcribing polymerase, implicating the polymerase itself as the vehicle which distributes AID on DNA as it moves away from the promoter.
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Replication fork stalling and cell cycle arrest in UV-irradiated Escherichia coli
TL;DR: This work investigated replication of UV-damaged DNA in Escherichia coli and found that ongoing replication stops for at least 15-20 min before resuming, raising the possibility that restart and lesion removal are coupled.
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The strong ADH1 promoter stimulates mitotic and meiotic recombination at the ADE6 gene of Schizosaccharomyces pombe.
TL;DR: Analysis of flanking marker configurations of prototrophic recombinants indicated that simple conversions as well as conversions associated with crossing over were stimulated in meiosis and the strongest stimulation of recombination was observed when the adh1 promoter was homozygous.
Journal ArticleDOI
Effect of Gene Induction on the Rate of Mutagenesis by ICR-191 in Escherichia coli
Robert K. Herman,Nomi B. Dworkin +1 more
TL;DR: It was concluded that some aspect of transcription or translation, or both, in the neighborhood of the I CR-191-induced mutation stimulated reversion by ICR-191, and this seemed to be an inherent difference in the original Lac(-) mutations.
Journal ArticleDOI
Sequence conservation at human and mouse orthologous common fragile regions, FRA3B/FHIT and Fra14A2/Fhit
Takeshi Shiraishi,Teresa Druck,Koshi Mimori,Jacob Flomenberg,Lori Berk,Hansjuerg Alder,Webb Miller,Kay Huebner,Carlo M. Croce +8 more
TL;DR: Comparison of orthologous fragile regions has identified highly conserved sequences with possible functional roles in maintenance of fragility in the human and mouse FRA3B and murine Fra14A2 locus.