The field of genome stability research has seen increasing attention in understanding how faithful DNA replication underpins the genetic integrity essential for cellular survival and organismal health. During each cell cycle, the replication machinery faces a range of intrinsic and extrinsic challenges, such as DNA lesions, unusual secondary DNA structures, protein-DNA crosslinks, shortages of building blocks, or mutations in essential replisome factors. These obstacles give rise to DNA replication stress, which is now recognized as a central driver in many diseases, most notably cancer. Advances in experimental and theoretical studies have highlighted that, although cells possess diverse surveillance and repair pathways to address replication stress, the precise mechanisms governing replication fork stability and preventing genome instability remain only partially understood. Recent research has uncovered a suite of novel factors and pathways that maintain fork dynamics and genome integrity, yet significant questions persist regarding their regulation and interplay during stress responses.
This Research Topic aims to unify current efforts exploring how replication stress responses and fork stability mechanisms contribute to genome maintenance. We seek to address key questions regarding the molecular players involved in fork reversal, stabilization, and the activation of checkpoint and repair pathways. By gathering novel studies, comprehensive reviews, and methodological advances, the aim is to unravel the complexity of replication stress responses, their relevance to human diseases—particularly cancer—and to foster discussion of emerging paradigms that may challenge conventional models.
This Research Topic will consider articles that address both fundamental and disease-relevant aspects of DNA replication stress, fork stability, and genome maintenance, with a primary emphasis on molecular mechanisms and regulatory pathways. The boundaries include mechanistic, cellular, and physiological perspectives, without extending into unrelated areas of genome dynamics.
We welcome contributions addressing, but not limited to, the following themes: • Origins and consequences of DNA replication stress • Dynamics and integrity of replication forks under stress • Regulatory factors and protein complexes in fork reversal and protection • Telomerase function and regulation in the context of replication stress • Connections between DNA replication stress and the onset or progression of human diseases, especially cancer • Development and application of innovative methods to study fork dynamics and genome stability
Article types and fees
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Brief Research Report
Editorial
FAIR² Data
General Commentary
Hypothesis and Theory
Methods
Mini Review
Opinion
Original Research
Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.
Article types
This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:
Brief Research Report
Editorial
FAIR² Data
General Commentary
Hypothesis and Theory
Methods
Mini Review
Opinion
Original Research
Perspective
Review
Technology and Code
Keywords: genome stability, dna replication, fork stability, genome maintenance
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.
