PIASγ Is Required for Faithful Chromosome Segregation in Human Cells

BACKGROUND: The precision of the metaphase-anaphase transition ensures stable genetic inheritance. The spindle checkpoint blocks anaphase onset until the last chromosome biorients at metaphase plate, then the bonds between sister chromatids are removed and disjoined chromatids segregate to the spindle poles. But, how sister separation is triggered is not fully understood. PRINCIPAL FINDINGS: We identify PIASγ as a human E3 sumo ligase required for timely and efficient sister chromatid separation. In cells lacking PIASγ, normal metaphase plates form, but the spindle checkpoint is activated, leading to a prolonged metaphase block. Sister chromatids remain cohered even if cohesin is removed by depletion of hSgo1, because DNA catenations persist at centromeres. PIASγ-depleted cells cannot properly localize Topoisomerase II at centromeres or in the cores of mitotic chromosomes, providing a functional link between PIASγ and Topoisomerase II. CONCLUSIONS: PIASγ directs Topoisomerase II to specific chromosome regions that require efficient removal of DNA catenations prior to anaphase. The lack of this activity activates the spindle checkpoint, protecting cells from non-disjunction. Because DNA catenations persist without PIASγ in the absence of cohesin, removal of catenations and cohesin rings must be regulated in parallel

The Plant Peptidome: An Expanding Repertoire of Structural Features and Biological Functions

Peptides fulfill a plethora of functions in plant growth, development, and stress responses. They act as key components of cell-to-cell communication, interfere with signaling and response pathways, or display antimicrobial activity. Strikingly, both the diversity and amount of plant peptides have been largely underestimated. Most characterized plant peptides to date acting as small signaling peptides or antimicrobial peptides are derived from nonfunctional precursor proteins. However, evidence is emerging on peptides derived from a functional protein, directly translated from small open reading frames (without the involvement of a precursor) or even encoded by primary transcripts of microRNAs. These novel types of peptides further add to the complexity of the plant peptidome, even though their number is still limited and functional characterization as well as translational evidence are often controversial. Here, we provide a comprehensive overview of the reported types of plant peptides, including their described functional and structural properties. We propose a novel, unifying peptide classification system to emphasize the enormous diversity in peptide synthesis and consequent complexity of the still expanding knowledge on the plant peptidome.status: publishe

Dynamic behavior of DNA topoisomerase IIβ in response to DNA double-strand breaks

DNA topoisomerase II (Topo II) is crucial for resolving topological problems of DNA and plays importantroles in various cellular processes, such as replication, transcription, and chromosome segregation.Although DNA topology problems may also occur during DNA repair, the possible involvement ofTopo II in this process remains to be fully investigated. Here, we show the dynamic behavior ofhuman Topo IIβ in response to DNA double-strand breaks (DSBs), which is the most harmful form ofDNA damage. Live cell imaging coupled with site-directed DSB induction by laser microirradiationdemonstrated rapid recruitment of EGFP-tagged Topo IIβ to the DSB site. Detergent extractionfollowed by immunofluorescence showed the tight association of endogenous Topo IIβ with DSB sites.Photobleaching analysis revealed that Topo IIβ is highly mobile in the nucleus. The Topo II catalyticinhibitors ICRF-187 and ICRF-193 reduced the Topo IIβ mobility and thereby prevented Topo IIβrecruitment to DSBs. Furthermore, Topo IIβ knockout cells exhibited increased sensitivity to bleomycinand decreased DSB repair mediated by homologous recombination (HR), implicating the role of Topo IIβin HR-mediated DSB repair. Taken together, these results highlight a novel aspect of Topo IIβ functionsin the cellular response to DSBs