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
Gene conversion between duplicated genetic elements in yeast
TL;DR: The results suggest that mitotic gene conversion may occur by a different pathway from that occurring in meiosis, and may be important in yeast mating type interconversion and the maintenance of sequence homogeneity in families of repeated eukaryotic genes.
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Ku70 Is Required for Late B Cell Development and Immunoglobulin Heavy Chain Class Switching
John P. Manis,Yansong Gu,Rusty Lansford,Eiichiro Sonoda,Roger Ferrini,Laurie Davidson,Klaus Rajewsky,Frederick W. Alt +7 more
TL;DR: It is concluded that Ku70 is required for the generation of B cells that have undergone Ig HC class switching, and potential roles for Ku70 in the CSR process are discussed.
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Recombination regulation by transcription-induced cohesin dissociation in rDNA Repeats
TL;DR: It is shown that amplification is dependent on transcription from a noncoding bidirectional promoter (E-pro) within the rDNA spacer, which stimulates the dissociation of cohesin, a DNA binding protein complex that suppresses sister-chromatid-based changes in rDNA copy number.
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Molecular Basis of Genetic Instability of Triplet Repeats
TL;DR: The discovery of expanding triplet repeats (or “mutable mutations”) in diseases showing anticipation afforded a physical basis for this unusual genetic phenomenon.
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Transcription-associated mutational asymmetry in mammalian evolution
TL;DR: A qualitatively different transcription-associated strand asymmetry in mammals is described, which may be a byproduct of transcription-coupled repair in germline cells, and can be used to detect the orientations and approximate extents of transcribed regions.