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Involvement of Variants in the Genes Encoding BRCA1-Associated Genome Surveillance Complex (BASC) in the Development of Human Common Diseases

Authors
  • Babushkina, N. P.1
  • Postrigan, A. E.1
  • Kucher, A. N.1
  • 1 Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, 634050, Russia , Tomsk (Russia)
Type
Published Article
Journal
Molecular Biology
Publisher
Pleiades Publishing
Publication Date
Mar 01, 2021
Volume
55
Issue
2
Pages
278–296
Identifiers
DOI: 10.1134/S0026893321020047
Source
Springer Nature
Keywords
License
Yellow

Abstract

AbstractThe “Mendelian code” hypothesis postulates a relationship between Mendelian (monogenic) and common pathologies. In this hypothesis, polymorphisms in the genes of Mendelian diseases may have a significant contribution to predisposition to common diseases in which the same biochemical pathways may be involved. In this review a group of genes encoding various proteins participating in the DNA repair, with a particular focus on the BRCA1-associated genome surveillance complex (BASC), is presented through the prism of the “Mendelian code” hypothesis. Here we discuss (1) their main functions in the repair of DNA double-strand breaks (ATM, MRE11, NBN, RAD50, BRCA1, and BLM) and mismatch repair (MSH2, MSH6, MLH1, PMS2, RF-C, and PCNA); (2) the mitochondrial involvement of these proteins; (3) the involvement of BASC proteins in the development of an adaptive immune response. For 13 out of 16 BASC protein encoding genes, mutations leading to monogenic diseases have already been described; for 11, there are associations with common diseases or individual biological processes. Patients with mutations in the genes of the BASC complex and patients with severe combined immunodeficiency share similar symptoms. Polymorphisms within DNA repair genes may play a role in the development of common diseases through the involvement of the immune response. The pleiotropic effects of these genes suggest their participation in the development of various conditions, both in health and pathology.

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