Research Topic

Chromosomal Fragile Sites, Genome Instability and Human Diseases

About this Research Topic

DNA replication is a key biological process in all organisms. During each cell division, numerous proteins and signaling pathways function together to ensure the complete duplication of the human genome. However, some genomic regions can raise specific problems for the replication machinery, leading to ...

DNA replication is a key biological process in all organisms. During each cell division, numerous proteins and signaling pathways function together to ensure the complete duplication of the human genome. However, some genomic regions can raise specific problems for the replication machinery, leading to chromosome breakage and genome instability. A large subset of these hard to replicate regions are referred to as fragile sites. Based on their frequency and replication timing, fragile sites are further classified as common fragile sites (CFSs), rare fragile sites (RFSs), or early replicating fragile sites (ERFs).

CFSs are widely studied and discussed in literature due to their prevalence, high frequency of breakage and their strong association with cancer. CFSs are chromosomal regions that are stable under normal conditions but display an increased rate of breakage under replication stress. In particular, they are preferential sites for chromosomal aberrations, viral DNA integration and are linked to the onset of oncogenesis and other disorders. The nature and cause of CFS fragility have been puzzling scientists for decades since their identification in 1984. The mechanisms responsible for CFS instability are hotly debated but different models all point to their inability to complete replication. In particular, factors such as late replication timing, the paucity of replication origins, DNA secondary structure formation, conflicts between replication forks and transcription machinery, microRNA genes and chromatin modification have been associated with CFS instability. Many proteins have been implicated in maintaining CFS stability as well. These include the DNA damage checkpoint kinase ATR, DNA repair proteins RAD51 and FANCD2, the RecQ family of helicases such as BLM, as well as the structure-specific endonuclease MUS81–EME1 and TRAIP.

Based on the complexity of CFSs, further studies focused on the interplay between the different postulated mechanisms would be extremely critical in gaining a better understanding of CFS stability. In addition, CFSs are important targets in human diseases, especially cancer research, since they are preferentially unstable from the early stages of human cancer development. The fragility of CFSs makes them hotspots for genomic rearrangements, resulting in tumor suppressor gene disruption and oncogene activation. Clarifying the mechanisms underlying CFS instability during tumorigenesis will further advance our understanding of cancer etiology and shed new light on cancer treatment.

We welcome Original Research, Review, Mini Review, Methods, Protocols, and Perspective articles related to fragile sites including:

  • Detection and analysis of chromosomal fragile sites;
  • Role of DNA replication and DNA damage repair, cell cycle checkpoints, epigenetics, genomic analysis, and cancer research.


    Keywords: fragile sites, replication stress, genome instability, cancers


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    Submission Deadlines

    26 April 2021 Manuscript

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    Manuscripts can be submitted to this Research Topic via the following journals:

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    Topic Editors

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    Submission Deadlines

    26 April 2021 Manuscript

    Participating Journals

    Manuscripts can be submitted to this Research Topic via the following journals:

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