Nuclear localization of the Saccharomyces cerevisiae ribonucleotide reductase small subunit requires a karyopherin and a WD40 repeat protein

Zhen Zhang, Xiuxiang An, Kui Yang, Deborah L. Perlstein, Leslie Hicks, Neil Kelleher, JoAnne Stubbe, Mingxia Huang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Ribonucleotide reductase (RNR) catalyzes the reduction of ribonucleotides to the corresponding deoxyribonucleotides and is an essential enzyme for DNA replication and repair. Cells have evolved intricate mechanisms to regulate RNR activity to ensure high fidelity of DNA replication during normal cell-cycle progression and of DNA repair upon genotoxic stress. The RNR holoenzyme is composed of a large subunit R1 (α, oligomeric state unknown) and a small subunit R2 (β2). R1 binds substrates and allosteric effectors; R2 contains a diferric-tyrosyl radical [(Fe)2-Y·] cofactor that is required for catalysis. In Saccharomyces cerevisiae, R1 is predominantly localized in the cytoplasm, whereas R2, which is a heterodimer (ββ′), is predominantly in the nucleus. When cells encounter DNA damage or stress during replication, ββ′ is redistributed from the nucleus to the cytoplasm in a checkpoint-dependent manner, resulting in the colocalization of R1 and R2. We have identified two proteins that have an important role in ββ′ nuclear localization: the importin β homolog Kap122 and the WD40 repeat protein Wtm1. Deletion of either WTM1 or KAP122 leads to loss of ββ′ nuclear localization. Wtm1 and its paralog Wtm2 are both nuclear proteins that are in the same protein complex with ββ′. Wtm1 also interacts with Kap122 in vivo and requires Kap122 for its nuclear localization. Our results suggest that Wtm1 acts either as an adaptor to facilitate nuclear import of ββ′ by Kap122 or as an anchor to retain ββ′ in the nucleus.

Original languageEnglish (US)
Pages (from-to)1422-1427
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number5
DOIs
StatePublished - Jan 31 2006

Keywords

  • DNA-damage checkpoint
  • Subcellular redistribution

ASJC Scopus subject areas

  • General

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