LAMMER kinase contributes to genome stability in Ustilago maydis.

Abstract

Here we report identification of the lkh1 gene encoding a LAMMER kinase homolog (Lkh1) from a screen for DNA repair-deficient mutants in Ustilago maydis. The mutant allele isolated results from a mutation at glutamine codon 488 to a stop codon that would be predicted to lead to truncation of the carboxy-terminal kinase domain of the protein. This mutant (lkh1(Q488*)) is highly sensitive to ultraviolet light, methyl methanesulfonate, and hydroxyurea. In contrast, a null mutant (lkh1Δ) deleted of the entire lkh1 gene has a less severe phenotype. No epistasis was observed when an lkh1(Q488*)rad51Δ double mutant was tested for genotoxin sensitivity. However, overexpressing the gene for Rad51, its regulator Brh2, or the Brh2 regulator Dss1 partially restored genotoxin resistance of the lkh1Δ and lkh1(Q488*) mutants. Deletion of lkh1 in a chk1Δ mutant enabled these double mutant cells to continue to cycle when challenged with hydroxyurea. lkh1Δ and lkh1(Q488*) mutants were able to complete the meiotic process but exhibited reduced heteroallelic recombination and aberrant chromosome segregation. The observations suggest that Lkh1 serves in some aspect of cell cycle regulation after DNA damage or replication stress and that it also contributes to proper chromosome segregation in meiosis.

• Authors: Carmen de Sena-Tomás, Jeanette H Sutherland, Mira Milisavljevic, Dragana B Nikolic, José Pérez-Martín, Milorad Kojic, William K Holloman
• Journal: DNA repair (DNA Repair (Amst)) Vol. 33 Pg. 70-7 (Sep 2015) ISSN: 1568-7856 [Electronic] Netherlands
• PMID: 26176563 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Fungal Proteins
• Methyl Methanesulfonate
• Protein Kinases
• Hydroxyurea

Topics

• Cell Cycle (drug effects)
• Chromosome Segregation (drug effects)
• Cloning, Molecular
• DNA Repair
• Epistasis, Genetic (drug effects)
• Fungal Proteins
• Genetic Complementation Test
• Genetic Testing
• Genomic Instability
• Hydroxyurea (pharmacology)
• Meiosis (drug effects)
• Methyl Methanesulfonate (pharmacology)
• Mutation (genetics)
• Phenotype
• Protein Kinases (metabolism)
• Recombination, Genetic (drug effects, genetics)
• Ultraviolet Rays
• Ustilago (cytology, drug effects, enzymology, genetics)