Condensin ATPase motifs contribute differentially to the maintenance of chromosome morphology and genome stability

Autor: Damien D’Amours, Mike Tyers, Rim Marrakchi, Mirela Pascariu, Thillaivillalan Dhanaraman, Roger Palou
Rok vydání: 2017
Předmět:
0301 basic medicine
Adenosine Triphosphatase
Cell division
Chromosomal Proteins
Non-Histone
Condensation
Condensin
ATPase
Gene Expression
Biochemistry
Database and Informatics Methods
Adenosine Triphosphate
ATP hydrolysis
Chemical reactions
Biology (General)
Adenosine Triphosphatases
Fluorescent in Situ Hybridization
Chromosome Biology
General Neuroscience
Physics
Hydrolysis
Condensed Matter Physics
Chromatin
Cell biology
Enzymes
DNA-Binding Proteins
Chemistry
Phenotypes
Premature chromosome condensation
Physical Sciences
Epigenetics
General Agricultural and Biological Sciences
Phase Transitions
Sequence Analysis
Research Article
Chromosome Structure and Function
Saccharomyces cerevisiae Proteins
QH301-705.5
Bioinformatics
Mitosis
Molecular Probe Techniques
macromolecular substances
Saccharomyces cerevisiae
Biology
Research and Analysis Methods
General Biochemistry
Genetics and Molecular Biology
Chromosomes
Genomic Instability
03 medical and health sciences
Sequence Motif Analysis
Genetics
Molecular Biology Techniques
Molecular Biology
General Immunology and Microbiology
Phosphatases
Chromosome
Biology and Life Sciences
Proteins
Cell Biology
Probe Hybridization
030104 developmental biology
Multiprotein Complexes
biology.protein
Enzymology
Cytogenetic Techniques
Genetic screen
Zdroj: PLoS Biology
PLoS Biology, Vol 16, Iss 6, p e2003980 (2018)
ISSN: 1545-7885
Popis: Effective transfer of genetic information during cell division requires a major reorganization of chromosome structure. This process is triggered by condensin, a conserved pentameric ATPase essential for chromosome condensation. How condensin harnesses the energy of ATP hydrolysis to promote chromatin reorganization is unknown. To address this issue, we performed a genetic screen specifically focused on the ATPase domain of Smc4, a core subunit of condensin. Our screen identified mutational hotspots that impair condensin’s ability to condense chromosomes to various degrees. These mutations have distinct effects on viability, genome stability, and chromosome morphology, revealing unique thresholds for condensin enzymatic activity in the execution of its cellular functions. Biochemical analyses indicate that inactivation of Smc4 ATPase activity can result in cell lethality because it favors a specific configuration of condensin that locks ATP in the enzyme. Together, our results provide critical insights into the mechanism used by condensin to harness the energy of ATP hydrolysis for the compaction of chromatin.
Author summary In eukaryotes, the deletion of a single copy of most genes shows little or no detectable phenotype under standard proliferative conditions. This implies that a large reduction in the level of a gene product can be tolerated by eukaryotic organisms and that a “reserve capacity” is built in the protein machinery that drives most cellular processes. Here, we test if the main effector of chromosome condensation—the condensin complex—operates with a reserve enzymatic capacity in the execution of its multiple functions in vivo. To achieve this, we created an allelic series of mutations that selectively inactivate condensin ATPase activity in a graded manner. We show that many core functions of condensin can be maintained even at low levels of ATPase activity. Our data also reveal the existence of various thresholds of ATPase activity that are necessary and sufficient for the execution of different cellular functions by condensin. Notably, loss of genome stability at repetitive DNA is only observed when condensin ATPase activity is severely impaired. Taken together, our results reveal key insights into the process of ATP hydrolysis by condensin and how the energy it releases promotes genome remodeling and stability during cell division.
Databáze: OpenAIRE
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