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
Transcription induces the formation of a stable RNA.DNA hybrid in the immunoglobulin alpha switch region.
TL;DR: It is demonstrated that the RNA.DNA hybrid is stable to both thermal and superhelical stress, tolerating temperatures in excess of 95 degrees C and restraining approximately 12 positive supercoils in the plasmid.
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Orientation dependence of trinucleotide CAG repeat instability in Saccharomyces cerevisiae.
TL;DR: Results suggest that the proximity of an ARS or another sequence has a profound effect on repeat stability, and that stability now depends on the orientation of ADE2 in the chromosome.
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Recombinant levels of Escherichia coli K-12 mutants deficient in various replication, recombination, or repair genes.
TL;DR: Analysis of the Lac+ recombinant formed by the various mutants indicated that they were identical to the recombinants formed by a wild-type strain, indicating that genetic recombination in E. coli is a highly regulated process involving multiple gene products.
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Interdependence between transcription and mRNP processing and export, and its impact on genetic stability
TL;DR: A tight interdependence among mRNP biogenesis steps and transcription and an unexpected effect of the nuclear exosome and the cleavage/polyadenylation factors on transcription elongation and genetic integrity are suggested.
Journal ArticleDOI
Activation-induced cytidine deaminase action is strongly stimulated by mutations of the THO complex
TL;DR: It is shown that AID action is transcription- dependent in yeast and that strong and transcription-dependent hypermutation and hyperrecombination are induced by AID if cells are deprived of THO, and proposed that a suboptimal cotranscriptional mRNP assembly at particular DNA regions could play an important role in Ig diversification and genome dynamics.