Essential functions of iron-requiring proteins in DNA replication, repair and cell cycle control.

Caiguo Zhang

doi:10.1007/s13238-014-0083-7

Abstract

Eukaryotic cells contain numerous iron-requiring proteins such as iron-sulfur (Fe-S) cluster proteins, hemoproteins and ribonucleotide reductases (RNRs). These proteins utilize iron as a cofactor and perform key roles in DNA replication, DNA repair, metabolic catalysis, iron regulation and cell cycle progression. Disruption of iron homeostasis always impairs the functions of these iron-requiring proteins and is genetically associated with diseases characterized by DNA repair defects in mammals. Organisms have evolved multi-layered mechanisms to regulate iron balance to ensure genome stability and cell development. This review briefly provides current perspectives on iron homeostasis in yeast and mammals, and mainly summarizes the most recent understandings on iron-requiring protein functions involved in DNA stability maintenance and cell cycle control.

Highlights

In most eukaryotic cells, iron is necessary to facilitate the assembly of functional Fe-S cluster proteins, heme-binding proteins, and ribonucleotide reductases (RNRs) (Dlouhy and Outten, 2013; Heath et al, 2013)
This review briefly provides current perspectives on iron homeostasis in yeast and mammals, and mainly summarizes the most recent understandings on iron-requiring protein functions involved in DNA stability maintenance and cell cycle control
These iron-requiring proteins are abundantly present in mitochondria, cytosol, and nucleus; such proteins diversely function in electron transfer, ribosome maturation, DNA replication and repair, and cell cycle control (Kaplan et al, 2006; Ye and Rouault, 2010; White and Dillingham, 2012)

Summary

INTRODUCTION

Iron is necessary to facilitate the assembly of functional Fe-S cluster proteins, heme-binding proteins, and ribonucleotide reductases (RNRs) (Dlouhy and Outten, 2013; Heath et al, 2013). Numerous proteins involved in DNA replication and repair require iron as a cofactor These proteins include the three DNA polymerases (Pol α, Pol δ and Pol ε), the DNA helicases (Rad3/XPD, Dna, RTEL1, FANCJ and ChlR1), and DNA primase regulator subunit Pri (PRIM2 in mammals). The yeast Irc, which shares similar hemebinding sites with Cyb, reportedly functions in chromatin remodeling and the increase of DNA damage foci (Alvaro et al, 2007) This result indicates that Irc may be involved in DNA replication process, and the assumption is supported by the genetic interactions of Irc with several DNA damage- and repair-related proteins, such as Pri, Pol, Dia, Rad, MMS22 and CDC13 in Saccharomyces genome database (SGD). No cell cycle regulation has been observed in RNR3 transcription (Lee and Elledge, 2006; Sanvisens et al, 2013)

SUMMARY

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