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

Review

Abstract

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.

Keywords

Cancers DNA lesions Double-strand DNA breaks Genetic disorders 

Abbreviations

DSB

Double-strand DNA break

DDR

DNA damage response

NER

Nucleotide excision repair

TLS

Translesion DNA synthesis

CNS

Central nervous system

ICL

Interstrand crosslink

HR

Homologous recombination

NHEJ

Non-homologous end-joining

Notes

Acknowledgements

We thank Dr. Margaret Biswas, from Edanz group (www.edanzediting.com/ac) for editing a draft of this manuscript.

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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