Version 1
: Received: 29 October 2024 / Approved: 30 October 2024 / Online: 30 October 2024 (13:54:12 CET)
How to cite:
Novoa-Aponte, L.; Leon-Torres, A.; Philpott, C. C. Guardians of the Genome: Iron-Sulfur Proteins in the Nucleus. Preprints2024, 2024102446. https://doi.org/10.20944/preprints202410.2446.v1
Novoa-Aponte, L.; Leon-Torres, A.; Philpott, C. C. Guardians of the Genome: Iron-Sulfur Proteins in the Nucleus. Preprints 2024, 2024102446. https://doi.org/10.20944/preprints202410.2446.v1
Novoa-Aponte, L.; Leon-Torres, A.; Philpott, C. C. Guardians of the Genome: Iron-Sulfur Proteins in the Nucleus. Preprints2024, 2024102446. https://doi.org/10.20944/preprints202410.2446.v1
APA Style
Novoa-Aponte, L., Leon-Torres, A., & Philpott, C. C. (2024). Guardians of the Genome: Iron-Sulfur Proteins in the Nucleus. Preprints. https://doi.org/10.20944/preprints202410.2446.v1
Chicago/Turabian Style
Novoa-Aponte, L., Andres Leon-Torres and Caroline C. Philpott. 2024 "Guardians of the Genome: Iron-Sulfur Proteins in the Nucleus" Preprints. https://doi.org/10.20944/preprints202410.2446.v1
Abstract
Iron-sulfur (Fe-S) clusters are essential cofactors found in many proteins in the mitochondria, cytosol, and nucleus of the cell. These versatile cofactors may undergo reversible oxidation-reduction reactions to enable electron transfers; they may be structural and confer stability to a folded protein; they may be regulatory and transduce an iron signal that alters the function or stability of a recipient protein. Of the nearly 70 proteins described in mammalian cells that bind Fe-S clusters, about half localize exclusively or partially to the nucleus, where they are required for DNA replication and repair, telomere maintenance, transcription, mitosis, and cell cycle control. Most nuclear Fe-S cluster proteins interact with DNA, including DNA polymerases, primase, helicases, and glycosylases. However, the specific roles of the clusters in the enzymatic activities of these proteins and their interplay with DNA remain a matter of debate. Defects in the metallation of nuclear Fe-S proteins cause genome instability and alter the regulation of cell division and proliferation, which are hallmarks of various genetic diseases and cancers. Here, we provide an inventory of the nuclear Fe-S cluster binding proteins and discuss cluster types, binding sites, the process of cluster acquisition, and potential roles of the cluster in the function of the proteins. However, many questions remain unresolved. We highlight critical gaps in our understanding of cluster delivery to nuclear client proteins, the potential for cluster repair, and the mechanistic roles that clusters play in these enzymes. Taken together, this review brings the focus to the nucleus of the human cell as a hotspot for Fe-S cluster proteins and aims to inspire new research in the roles of iron in DNA metabolism and the maintenance of genome integrity.
Keywords
Iron-sulfur cluster; nucleus; iron trafficking; DNA replication; DNA repair
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
