Spd2 assists Spd1 in modulation of RNR architecture but does not regulate deoxynucleotide pools

Vejrup-Hansen, Rasmus, Fleck, Oliver, Landvad, Katrine, Fahnøe, Ulrik, Broendum, Sebastian S, Schreurs, Ann-Sofie, Kragelund, Birthe B, Carr, Antony M, Holmberg, Christian and Nielsen, Olaf (2014) Spd2 assists Spd1 in modulation of RNR architecture but does not regulate deoxynucleotide pools. Journal of Cell Science, 127. pp. 2460-2470. ISSN 0021-9533

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Abstract

In yeasts, small intrinsically disordered proteins (IDPs) modulate ribonucleotide reductase (RNR) activity to ensure an optimal supply of dNTPs for DNA synthesis. The S. pombe Spd1 protein can directly inhibit the large RNR subunit (R1), import the small subunit (R2) into the nucleus and induce an architectural change in the R1-R2 holocomplex. Here, we report the characterization of Spd2, a protein with homology to Spd1. We show that Spd2 is a CRL4Cdt2 controlled IDP that functions together with Spd1 in the DNA damage response and in modulation of RNR architecture. However, Spd2 does not regulate dNTP pools and R2 nuclear import. Furthermore, deletion of spd2 only weakly suppresses the Rad3ATR checkpoint dependency of CRL4Cdt2 mutants. However, when we raised intracellular dNTP pools by inactivation of RNR feedback inhibition, deletion of spd2 could suppress the checkpoint dependency of CRL4Cdt2 mutant cells to the same extent as spd1. Collectively, these observations suggest that Spd1 on its own regulates dNTP pools, while it together with Spd2 modulates RNR architecture and sensitizes cells to DNA damage.

Item Type: Article
Additional Information: Running title: spd2 in fission yeast
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science > QD Chemistry > QD0241 Organic chemistry > QD0415 Biochemistry
Depositing User: Gee Wheatley
Date Deposited: 28 Apr 2014 14:15
Last Modified: 12 Mar 2017 06:38
URI: http://sro.sussex.ac.uk/id/eprint/48303

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