DNA replication is an essential nuclear process for genome stability maintenance. Physical barriers and difficult-to-replicate regions hinder replication fork progression and threaten the fidelity of DNA replication. Interstrand crosslinks, DNA-protein crosslinks, DNA secondary structures, and regions of active transcription interfere with helix unwinding and DNA synthesis. Some barriers are naturally occurring and have a physiological role, while others, such as interstrand and DNA-protein crosslinks, form after exposure to damaging agents and need prompt repair. Pausing or stalling the replication machinery at these obstacles can result in fork collapse and the formation of toxic breaks. Due to their heterogeneous nature, these barriers are sensed, resolved, and/or bypassed in different ways. However, if they are not resolved and the consequent DNA damage is not timely and efficiently repaired, they will lead to irreversible genomic instability and will consequently trigger carcinogenesis.
Studies on replication barriers spark growing interest in the context of cancer therapy, as cancer cells heavily rely on DNA replication. Factors required for resolving and bypassing these obstacles become potential chemotherapy targets, but we are far from having a comprehensive understanding of the basic molecular mechanisms. The list of specific assays and methods to detect these barriers in cells is growing. These tools will be instrumental in identifying the factors that play a role in the response to replicative stress, as they will allow the identification of novel therapies for cancer.
In this Research topic, we will widely address replication barrier sensing, resolution, and bypass, with regard to the cellular response and factors involved, detection methods, and their limitations. We welcome original research, review articles, and technical manuscripts covering these topics:
• detection methods in cells
• signaling during DNA replication
• the role of non-coding RNAs in replication stress
• sensing and bypassing of DNA secondary structures and R-loops
• repair of interstrand crosslinks and DNA-protein crosslinks
• identification of novel factors involved in the response to replication stress and their use as potential biomarkers of cancer
• druggable targets and exploitation of defects in sensing and repair for chemotherapy
We accept different article types including Original Research articles, Mini-Reviews, Brief Research Reports, and Perspectives. A full list of accepted article types, including descriptions, can be found at this
link.