Publications (40) View all
-
Article: Genome stability roles of SUMO-targeted ubiquitin ligases.
[show abstract] [hide abstract]
ABSTRACT: Post-translational modification of the cell's proteome by ubiquitin and ubiquitin-like proteins provides dynamic functional regulation. Ubiquitin and SUMO are well-studied post-translational modifiers that typically impart distinct effects on their targets. The recent discovery that modification by SUMO can target proteins for ubiquitination and proteasomal degradation sets a new paradigm in the field, and offers insights into the roles of SUMO and ubiquitin in genome stability.DNA Repair 03/2009; 8(4):517-24. · 4.14 Impact Factor -
Article: DNA replication checkpoint.
Current Biology 12/2001; 11(23):R953-6. · 9.65 Impact Factor -
Article: Mus81-Eme1 are essential components of a Holliday junction resolvase.
[show abstract] [hide abstract]
ABSTRACT: Mus81, a fission yeast protein related to the XPF subunit of ERCC1-XPF nucleotide excision repair endonuclease, is essential for meiosis and important for coping with stalled replication forks. These processes require resolution of X-shaped DNA structures known as Holliday junctions. We report that Mus81 and an associated protein Eme1 are components of an endonuclease that resolves Holliday junctions into linear duplex products. Mus81 and Eme1 are required during meiosis at a late step of meiotic recombination. The mus81 meiotic defect is rescued by expression of a bacterial Holliday junction resolvase. These findings constitute strong evidence that Mus81 and Eme1 are subunits of a nuclear Holliday junction resolvase.Cell 12/2001; 107(4):537-48. · 32.40 Impact Factor -
Article: Human Mus81-associated endonuclease cleaves Holliday junctions in vitro.
[show abstract] [hide abstract]
ABSTRACT: Mus81, a protein with homology to the XPF subunit of the ERCC1-XPF endonuclease, is important for replicational stress tolerance in both budding and fission yeast. Human Mus81 has associated endonuclease activity against structure-specific oligonucleotide substrates, including synthetic Holliday junctions. Mus81-associated endonuclease resolves Holliday junctions into linear duplexes by cutting across the junction exclusively on strands of like polarity. In addition, Mus81 protein abundance increases in cells following exposure to agents that block DNA replication. Taken together, these findings suggest a role for Mus81 in resolving Holliday junctions that arise when DNA replication is blocked by damage or by nucleotide depletion. Mus81 is not related by sequence to previously characterized Holliday junction resolving enzymes, and it has distinct enzymatic properties that suggest it uses a novel enzymatic strategy to cleave Holliday junctions.Molecular Cell 12/2001; 8(5):1117-27. · 14.18 Impact Factor -
Article: Threonine-11, phosphorylated by Rad3 and atm in vitro, is required for activation of fission yeast checkpoint kinase Cds1.
[show abstract] [hide abstract]
ABSTRACT: Fission yeast Cds1 is phosphorylated and activated when DNA replication is interrupted by nucleotide starvation or DNA damage. Cds1 enforces the S-M checkpoint that couples mitosis (M) to the completion of DNA synthesis (S). Cds1 also controls replicational stress tolerance mechanisms. Cds1 is regulated by a group of proteins that includes Rad3, a kinase related to human checkpoint kinase ATM (ataxia telangiectasia mutated). ATM phosphorylates serine or threonine followed by glutamine (SQ or TQ). Here we show that in vitro, Rad3 and ATM phosphorylate the N-terminal domain of Cds1 at the motif T(11)Q(12). Substitution of threonine-11 with alanine (T11A) abolished Cds1 activation that occurs when DNA replication is inhibited by hydroxyurea (HU) treatment. The cds1-T11A mutant was profoundly sensitive to HU, although not quite as sensitive as a cds1(-) null mutant. Cds1(T11A) was unable to enforce the S-M checkpoint. These results strongly suggest that Rad3-dependent phosphorylation of Cds1 at threonine-11 is required for Cds1 activation and function.Molecular and Cellular Biology 06/2001; 21(10):3398-404. · 5.53 Impact Factor
