Importance of Germline and Somatic Alterations in Human MRE11, RAD50, and NBN Genes Coding for MRN Complex

0571430 - ÚMG 2024 RIV CH eng J - Článek v odborném periodiku
Otahalová, B. - Volková, Z. - Soukupová, J. - Kleiblová, P. - Janatová, M. - Vočka, M. - Macůrek, Libor - Kleibl, Z.
Importance of Germline and Somatic Alterations in Human MRE11, RAD50, and NBN Genes Coding for MRN Complex.
International Journal of Molecular Sciences. Roč. 24, č. 6 (2023), č. článku 5612. ISSN 1661-6596
Grant CEP: GA MZd NU22-03-00276; GA MŠMT LX22NPO5102
Institucionální podpora: RVO:68378050
Klíčová slova: atld * DNA repair * hereditary cancer syndromes * mre11 * nbn * nbs * nbsld * ngs * rad50 * tp53 * variant interpretation
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 5.6, rok: 2022
Způsob publikování: Open access
https://www.mdpi.com/1422-0067/24/6/5612

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.
Trvalý link: https://hdl.handle.net/11104/0342653