PIASγ Is Required for Faithful Chromosome Segregation in Human Cells

Díaz-Martínez, Laura A.; Giménez-Abián, Juan F.; Azuma, Yoshiaki; Guacci, Vincent; Giménez-Martín, G.; Lanier, Lorene M.; Clarke, Duncan J.

doi:10.1371/journal.pone.0000053

Cited by 70 publications

(101 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In vertebrates, disruption of PIAS␥ or RanBP2, two SUMO ligases implicated in Topo II sumoylation, interferes with Topo II localization to CENs and chromatid separation in anaphase (Azuma et al, 2005;Diaz-Martinez et al, 2006;Dawlaty et al, 2008). It is not known whether Top2 is targeted to yeast CENs in an equivalent manner.…”

Section: Discussionmentioning

confidence: 99%

“…A model in which Top2 enforces the sensitivity of the tension checkpoint would seem to contrast with reports indicating perturbations to Topo II activate metaphase arrest through pathways that overlap extensively, if are not identical to, the SAC (Mikhailov et al, 2002;Skoufias et al, 2004;Clarke et al, 2006;Diaz-Martinez et al, 2006;Toyoda and Yanagida, 2006). The signal(s) that elicits this arrest has been controversial, with one suggestion being unresolved cate-nates activate a Topo II-responsive checkpoint (Skoufias et al, 2004;Clarke et al, 2006).…”

Section: Top2 Function In the Tension Checkpointmentioning

confidence: 97%

“…First, a primary function for Topo II at CENs, at least in vertebrates, seems to be untangling sister CENs as cells transition into anaphase (Downes al., 1991;Shamu and Murray, 1992;Clarke et al, 1993;Azuma et al, 2005;Diaz-Martinez et al, 2006;Dawlaty et al, 2008). Second, our previous work suggested Top2 might mediate a cohesive linkage between sister CENs that was potentially distinct from catenation.…”

Section: Cen Superhelicity In Top2 Mutantsmentioning

confidence: 99%

“…First, in vertebrates Topo II accumulates and exhibits robust activity within mitotic CEN chromatin (reviewed in Porter and Farr, 2004). Sumoylation of Topo II (or possibly other substrates) plays an as yet undefined role in controlling Topo II localization to CENs (Azuma et al, 2005;Diaz-Martinez et al, 2006;Dawlaty et al, 2008). Treatments that block this modification also perturb sister chromatid separation during anaphase, suggesting Topo II CEN targeting helps resolve a final population of topological intertwinings (catenates) so sister CENs can disjoin efficiently.…”

mentioning

confidence: 99%

“…Second, in both yeast and vertebrates, Topo II inhibition can restore chromatid attachment to the spindle and silence the tension checkpoint in cohesin mutants, an effect that may be attributable to unresolved catenates substituting for cohesin in generating tension (Dewar et al, 2004;Vagnarelli et al, 2004;Toyoda and Yanagida, 2006). Third, perturbations to Topo II can in some cases activate Ipl1/Aurora-B-dependent preanaphase arrest Diaz-Martinez et al, 2006). This has suggested Ipl1/Aurora-B may be involved in monitoring some aspect of Topo II function, but the basis for this surveillance has remained unclear.…”

mentioning

confidence: 99%

See 4 more Smart Citations

DNA Topoisomerase II Is a Determinant of the Tensile Properties of Yeast Centromeric Chromatin and the Tension Checkpoint

Warsi

Navarro

Bachant

2008

MBoC

View full text Add to dashboard Cite

Centromeric (CEN) chromatin is placed under mechanical tension and stretches as kinetochores biorient on the mitotic spindle. This deformation could conceivably provide a readout of biorientation to error correction mechanisms that monitor kinetochore-spindle interactions, but whether CEN chromatin acts in a tensiometer capacity is unresolved. Here, we report observations linking yeast Topoisomerase II (Top2) to both CEN mechanics and assessment of interkinetochore tension. First, in top2-4 and sumoylation-resistant top2-SNM mutants CEN chromatin stretches extensively during biorientation, resulting in increased sister kinetochore separation and preanaphase spindle extension. Our data indicate increased CEN stretching corresponds with alterations to CEN topology induced in response to tension. Second, Top2 potentiates aspects of the tension checkpoint. Mutations affecting the Mtw1 kinetochore protein activate Ipl1 kinase to detach kinetochores and induce spindle checkpoint arrest. In mtw1top2-4 and mtw1top2-SNM mutants, however, kinetochores are resistant to detachment and checkpoint arrest is attenuated. For top2-SNM cells, CEN stretching and checkpoint attenuation occur even in the absence of catenation linking sister chromatids. In sum, Top2 seems to play a novel role in CEN compaction that is distinct from decatenation. Perturbations to this function may allow weakened kinetochores to stretch CENs in a manner that mimics tension or evades Ipl1 surveillance. INTRODUCTIONAccurate chromosome segregation requires that sister kinetochores connect to microtubules from opposing poles of the mitotic spindle, a process known as biorientation. Misaligned kinetochore attachments can also occur, and they must be resolved to prevent lethal chromosome segregation errors or the formation of aneuploid cells. Syntelic attachments arise when sister kinetochores connect to microtubules from the same spindle pole; merotelic attachments result if a single kinetochore attaches to both poles. The Aurora-B kinases, complexed with conserved INCENP/ Sli15 and Survivin/Bir1 subunits of the chromosomal passenger complex, are key regulators of the error correction machinery that resolves such inappropriate attachments (reviewed in Ruchaud et al., 2007). Aurora-B (Ipl1 in budding yeast) facilitates error correction through two mechanisms. First, these kinases destabilize defective kinetochore-microtubule interactions by phosphorylating kinetochore-associated proteins. Second, Ipl1/Aurora-B plays a role in activating the spindle assembly checkpoint (SAC), both in response to syntelic attachments as well as mutations that affect the kinetochore or sister chromatid cohesion. Checkpoint activation may occur indirectly because Ipl1/Aurora-B creates unoccupied kinetochores (Pinsky et al., 2006) or directly through phosphorylation of SAC regulators (King et al., 2007).The manner in which Ipl1/Aurora-B distinguishes such a wide range of spindle lesions is not well understood. With the exception of merotelic interactions (Cimini, 2007), those att...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Top2 Function In the Tension Checkpointmentioning

confidence: 97%

Section: Cen Superhelicity In Top2 Mutantsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

DNA Topoisomerase II Is a Determinant of the Tensile Properties of Yeast Centromeric Chromatin and the Tension Checkpoint

Warsi

Navarro

Bachant

2008

MBoC

View full text Add to dashboard Cite

show abstract

Chromosome Condensation and Cohesion

Díaz-Martínez

2010

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

The diploid human genome consists of 46 chromosomes, which collectively contain about 2 m of deoxyribonucleic acid (DNA). During mitosis, the genome is packaged into 46 pairs of sister chromatids, each less than 10 μm long. Two fundamental mechanisms govern the formation and maintenance of chromosome structure during mitosis: (i) the dramatic and progressive compaction of chromosomes in the process of chromosome condensation and (ii) the establishment of the physical linkages or cohesion between the sister chromatids. Central to the processes of chromosome condensation and cohesion are the type II topoisomerases and the Structure Maintenance of Chromosomes (SMC) family of proteins, which form the condensin and cohesin complexes. These proteins cooperate to ensure chromosome condensation and cohesion, thus promoting the accurate partition of the genome during mitosis. Key Concepts: Chromosome condensation and cohesion are necessary for accurate chromosome segregation. Condensin and topoisomerase IIα are the major regulators of chromosome condensation. Sister‐chromatid cohesion is required for the bipolar attachment of chromosomes to the spindle microtubules and counteracts the spindle pulling forces generated at the kinetochores. The cohesin complex is critical for sister‐chromatid cohesion. Both DNA catenation and sister‐chromatid cohesion have to be resolved for proper sister‐chromatid separation. Centromeric cohesion is regulated by the spindle checkpoint. Its removal occurs at the onset of anaphase.

show abstract

Targeting the Sumoylation Pathway

Pungaliya¹,

Rubin²

2009

Modulation of Protein Stability in Cancer Therapy

View full text Add to dashboard Cite

PIASγ Is Required for Faithful Chromosome Segregation in Human Cells

Cited by 70 publications

References 48 publications

DNA Topoisomerase II Is a Determinant of the Tensile Properties of Yeast Centromeric Chromatin and the Tension Checkpoint

DNA Topoisomerase II Is a Determinant of the Tensile Properties of Yeast Centromeric Chromatin and the Tension Checkpoint

Chromosome Condensation and Cohesion

Targeting the Sumoylation Pathway

Contact Info

Product

Resources

About