Cell Biology and Toxicology

, Volume 34, Issue 5, pp 337–350 | Cite as

Genome instability syndromes caused by impaired DNA repair and aberrant DNA damage responses

  • Takeshi Terabayashi
  • Katsuhiro Hanada


Maintenance of genome integrity is essential for all organisms because genome information regulates cell proliferation, growth arrest, and vital metabolic processes in cells, tissues, organs, and organisms. Because genomes are constantly exposed to intrinsic and extrinsic genotoxic stress, cellular DNA repair machinery and proper DNA damage responses (DDR) have evolved to quickly eliminate genotoxic DNA lesions, thus maintaining the genome integrity suitably. In human, germline mutations in genes involved not only in cellular DNA repair pathways but also in cellular DDR machinery frequently predispose hereditary diseases associated with chromosome aberrations. These genetic syndromes typically displaying mutations in DNA repair/DDR-related genes are often called “genome instability syndromes.” Common features of these hereditary syndromes include a high incidence of cancers and developmental abnormalities including short stature, microcephaly, and/or neurological deficiencies. However, precisely how impaired DNA repair and/or dysfunctional DDR pathologically promote(s) these syndromes are poorly understood. In this review article, we summarize the clinical symptoms of several representatives “genome instability syndromes” and propose the plausible pathogenesis thereof.


Cancers DNA lesions Double-strand DNA breaks Genetic disorders 



Double-strand DNA break


DNA damage response


Nucleotide excision repair


Translesion DNA synthesis


Central nervous system


Interstrand crosslink


Homologous recombination


Non-homologous end-joining



We thank Dr. Margaret Biswas, from Edanz group ( for editing a draft of this manuscript.


This study is partially funded by the Practical Research Project for Rare/ Intractable Diseases, Japan Agency for Medical Research and Development, AMED to KH; a Grant-in-Aid for Scientific Research (C) (grant number 16K07119), Japan Society for the Promotion of Science (JSPS), The Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan to TT.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Authors and Affiliations

  1. 1.Department of Pharmacology, Faculty of MedicineOita UniversityYufuJapan
  2. 2.Clinical Engineering Research Center, Faculty of MedicineOita UniversityYufuJapan

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