The MRE11, RAD50, and NBN genes encode for the nuclear MRN protein complex, which senses the DNA double strand breaks and initiates the DNA repair. The MRN complex also participates in the activation of ATM kinase, which coordinates DNA repair with the p53-dependent cell cycle checkpoint arrest. Carriers of homozygous germline pathogenic variants in the MRN complex genes or compound heterozygotes develop phenotypically distinct rare autosomal recessive syndromes characterized by chromosomal instability and neurological symptoms. Heterozygous germline alterations in the MRN complex genes have been associated with a poorly-specified predisposition to various cancer types. Somatic alterations in the MRN complex genes may represent valuable predictive and prognostic biomarkers in cancer patients. MRN complex genes have been targeted in several next-generation sequencing panels for cancer and neurological disorders, but interpretation of the identified alterations is challenging due to the complexity of MRN complex function in the DNA damage response. In this review, we outline the structural characteristics of the MRE11, RAD50 and NBN proteins, the assembly and functions of the MRN complex from the perspective of clinical interpretation of germline and somatic alterations in the MRE11, RAD50 and NBN genes.

• Klíčová slova
• ATLD, DNA repair, MRE11, NBN, NBS, NBSLD, NGS, RAD50, TP53, hereditary cancer syndromes, variant interpretation,
• MeSH
• ATM protein genetika   metabolismus   MeSH
• DNA vazebné proteiny genetika   metabolismus   MeSH
• enzymy opravy DNA genetika   metabolismus   MeSH
• homologní protein MRE11 genetika   metabolismus   MeSH
• hydrolasy působící na anhydridy kyselin genetika   metabolismus   MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• lidé MeSH
• nádorové supresorové proteiny * genetika   MeSH
• oprava DNA genetika   MeSH
• proteiny buněčného cyklu * metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• ATM protein MeSH
• DNA vazebné proteiny MeSH
• enzymy opravy DNA MeSH
• homologní protein MRE11 MeSH
• hydrolasy působící na anhydridy kyselin MeSH
• jaderné proteiny MeSH
• nádorové supresorové proteiny * MeSH
• NBN protein, human MeSH Prohlížeč
• proteiny buněčného cyklu * MeSH
• RAD50 protein, human MeSH Prohlížeč