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 Effect of DNA Replication Mutations on CAG Tract Stability in Yeast
TL;DR: Results show that while CAG repeats are destabilized by many of the same mutations that destabilize other simple repeats, they also have some behaviors that are suggestive of their potential to form hairpin structures.
Journal ArticleDOI
Expanded CAG repeats activate the DNA damage checkpoint pathway.
TL;DR: A novel finding that expanded CAG repeats activate the DNA damage response is reported, indicating that components of the checkpoint machinery play an active role in the maintenance of both chromosomal integrity and repeat stability at expanded C AG sequences.
Journal ArticleDOI
Error-free Recombinational Repair Predominates over Mutagenic Translesion Replication in E. coli
TL;DR: It is shown that RR effectively repairs gaps opposite DNA lesions in E. coli when both mechanisms are functional, and predominance of RR predominates over TLR, being responsible for 86% of the repair events.
Book ChapterDOI
The role of activation-induced deaminase in antibody diversification and chromosome translocations.
Almudena R. Ramiro,Bernardo Reina San-Martin,Kevin M. McBride,Mila Jankovic,Vasco M. Barreto,André Nussenzweig,Michel C. Nussenzweig,Michel C. Nussenzweig +7 more
TL;DR: How the B-cell specific molecular events required for immunoglobulin class switch recombination are initiated and how they contribute to chromosome translocations in vivo are reviewed are reviewed.