About this Research Topic
Strict, efficient and error-free regulation of DNA replication is key to promote faithful genome propagation in dividing cells. Genetic instability refers to a range of genetic alterations which can drive evolution at the molecular level, but are also associated with pathological disorders, such as cancer, premature aging and neurodegeneration.
The mechanisms leading to genomic instability are varied, depending mainly on the type of DNA lesion and the potential for mistakes and imprecisions associated with their repair. A vast array of different DNA lesions need to be recognized, signaled and repaired, often by intricate assemblies of numerous proteins and orchestrated by a complex cascade of post-translational modifications.
One major source of genome instability is DNA replication stress, which is caused by DNA damage, secondary DNA structures or any other obstruction to the progression of the DNA replication fork, and is thought to contribute substantially to the oncogenic process. To counteract this threat, the DNA damage response (DDR) signals the presence of DNA lesions or aberrant replication structures, in order to protect stalled replication forks and facilitate the completion of replication, thus guaranteeing the maintenance of genome stability.
Chromosome ends are protected by the telomere complex. Whilst telomere shortening can exert a tumor-suppressive role through proliferation arrest caused by the activation of DDR-kinases ATM and ATR at unprotected ends, loss of telomere protection can lead to telomere crisis. Genome instability in cells undergoing telomere crisis can give rise to substantial genomic rearrangements, such as aneuploidy, translocations, whole-genome duplication, chromothripsis and kataegis.
In this Research Topic, we aim to give a comprehensive overview of the current understanding of genome instability, DNA damage signaling and repair, replication stress, and telomere biology. The goal is to understand (1) how new and/or updated methods and technologies can facilitate the study of the complex mechanisms involved in the maintenance of genomic stability; (2) how those methods can be used in basic research and clinical studies for diagnosis and treatments strategies of diseases associated with genome instability, and finally, (3) to explore technologies which will unveil new knowledge in the genome instability field.
We welcome Original Research and Review articles covering new and updated technologies in the following areas:
• Fundamental mechanisms of genome instability and DDR;
• Maintenance of genome stability;
• Fundamental mechanisms of replication stress and telomere crisis;
• Biological consequences of genome instability, DDR and DNA repair deficiencies;
• Genome instability in early development and ageing processes;
• Translational research of early diagnosis and therapeutic opportunities.
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.