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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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
Replication stalling at Friedreich's ataxia (GAA)n repeats in vivo.
TL;DR: Friedreich's ataxia (GAA) n repeats of various lengths were cloned into a Saccharymyces cerevisiae plasmid, and their effects on DNA replication were analyzed using two-dimensional electrophoresis of replication intermediates to believe that repeat-caused replication attenuation in vivo is due to triplex formation.
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Smc5-Smc6 mediate DNA double-strand-break repair by promoting sister-chromatid recombination.
Giacomo De Piccoli,Felipe Cortés-Ledesma,Gregory Ira,Gregory Ira,Jordi Torres-Rosell,Stefan Uhle,Sarah Farmer,Ji-Young Hwang,Félix Machín,Audrey Ceschia,Alexandra McAleenan,Violeta Cordon-Preciado,Andrés Clemente-Blanco,Felip Vilella-Mitjana,Pranav Ullal,Adam Jarmuz,Beatriz Leitao,Debra A. Bressan,Farokh Dotiwala,Alma Papusha,Xiaolan Zhao,Kyungjae Myung,James E. Haber,Andrés Aguilera,Luis Aragón +24 more
TL;DR: The findings show that the Smc5–Smc6 complex is essential for genome stability as it promotes repair of DSBs by error-free sister-chromatid recombination (SCR), thereby suppressing inappropriate non-sister recombination events.
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RNA: DNA complex formation upon transcription of immunoglobulin switch regions: implications for the mechanism and regualtion of class switch recombination
TL;DR: It is found that cell-free transcription of repetitive murine switch regions (Smu, S gamma 2b and S gamma 3) leads to altered DNA mobility on agarose gels, and this results suggest a general model involving an RNA:DNA complex as an intermediate during class switch recombination.
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Chromosome segregation and genomic stability
TL;DR: The ubiquity of aneuploidy in human cancers, particularly solid tumors, suggests a fundamental link between errors in chromosome segregation and tumorigenesis.
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The S. cerevisiae Rrm3p DNA helicase moves with the replication fork and affects replication of all yeast chromosomes
TL;DR: It is shown that replication of all yeast chromosomes was markedly delayed in rrm3 cells, suggesting that although Rrm3p has a global role in DNA replication, its activity is needed only or primarily at specific, difficult toreplicate sites.