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Biochim Biophys Acta. 2015 Jun;1853(6):1253-71. doi: 10.1016/j.bbamcr.2015.01.018. Epub 2015 Feb 2.

Emerging critical roles of Fe-S clusters in DNA replication and repair.

Author information

1
Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA. Electronic address: jfuss@lbl.gov.
2
Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA.
3
Life Sciences Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA; Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA. Electronic address: jatainer@lbl.gov.

Abstract

Fe-S clusters are partners in the origin of life that predate cells, acetyl-CoA metabolism, DNA, and the RNA world. The double helix solved the mystery of DNA replication by base pairing for accurate copying. Yet, for genome stability necessary to life, the double helix has equally important implications for damage repair. Here we examine striking advances that uncover Fe-S cluster roles both in copying the genetic sequence by DNA polymerases and in crucial repair processes for genome maintenance, as mutational defects cause cancer and degenerative disease. Moreover, we examine an exciting, controversial role for Fe-S clusters in a third element required for life - the long-range coordination and regulation of replication and repair events. By their ability to delocalize electrons over both Fe and S centers, Fe-S clusters have unbeatable features for protein conformational control and charge transfer via double-stranded DNA that may fundamentally transform our understanding of life, replication, and repair. This article is part of a Special Issue entitled: Fe/S proteins: Analysis, structure, function, biogenesis and diseases.

KEYWORDS:

Cancer and degenerative disease; DNA charge transfer communication; DNA repair; DNA replication; Fe–S cluster; Genome integrity

PMID:
25655665
PMCID:
PMC4576882
DOI:
10.1016/j.bbamcr.2015.01.018
[Indexed for MEDLINE]
Free PMC Article

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