RESUMEN
Three human nucleases, SNM1A, SNM1B/Apollo, and SNM1C/Artemis, belong to the SNM1 gene family. These nucleases are involved in various cellular functions, including homologous recombination, nonhomologous end-joining, cell cycle regulation, and telomere maintenance. These three proteins share a similar catalytic domain, which is characterized as a fused metallo-ß-lactamase and a CPSF-Artemis-SNM1-PSO2 domain. SNM1A and SNM1B/Apollo are exonucleases, whereas SNM1C/Artemis is an endonuclease. This review contains a summary of recent research on SNM1's cellular and biochemical functions, as well as structural biology studies. In addition, protein structure prediction by the artificial intelligence program AlphaFold provides a different view of the proteins' non-catalytic domain features, which may be used in combination with current results from X-ray crystallography and cryo-EM to understand their mechanism more clearly.
Asunto(s)
Enzimas Reparadoras del ADN , Reparación del ADN , Humanos , Inteligencia Artificial , Enzimas Reparadoras del ADN/genética , Enzimas Reparadoras del ADN/metabolismo , Endonucleasas/genética , Endonucleasas/metabolismo , Exodesoxirribonucleasas/genética , Exodesoxirribonucleasas/metabolismo , Proteínas Nucleares/metabolismo , Proteínas de Ciclo Celular/metabolismoRESUMEN
Approximately 90% of all human cancers, in which some deregulation of cell cycle arrest or programmed cell death has occurred, express telomerase, a ribonucleoprotein whose activity is normally turned off in healthy somatic tissues. Additionally, small populations of self-renewing stem cells, such as hematopoietic stem cells, skin and hair follicle basal layer cells and intestinal basal crypt cells, have been shown to retain telomerase activity. Conversely, hereditary defects that result in shortened telomeres in humans have been shown to manifest most often as bone marrow failure or pulmonary fibrosis, along with a myriad of other symptoms, likely due to the loss of the stem and/or progenitor cells of affected tissues. The aim of this review is to highlight our knowledge of the mechanisms of telomere maintenance that contribute to the pathology of human disease caused by dysfunctional telomere homeostasis. Specifically, a new role for the SNM1B/Apollo nuclease in the pathologies of Hoyeraal-Hreidarsson syndrome will be discussed.