PICH and TOP3A cooperate to induce positive DNA supercoiling

Bizard, Anna H.; Allemand, Jean-François; Hassenkam, Tue; Paramasivam, Manikandan; Sarlós, Kata; Singh, Manika Indrajit; Hickson, Ian D.

doi:10.1038/s41594-019-0201-6

Cited by 35 publications

(47 citation statements)

References 42 publications

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“…This supercoiling reaction is driven by the ability of PICH to act as a translocating topological barrier and to redistribute torsional stress on a dsDNA substrate, in the same manner as discussed above in the context of the twin supercoiling domain model ( Figure 1A). Unexpectedly, PICH was shown to extrude DNA loops concomitant with this torsional stress redistribution, such that negative supercoils are able to accumulate in the extruded loop located in its wake, while the rest of the substrate becomes progressively more positively supercoiled (96). Such a loop extrusion mechanism enables PICH to promote the local melting of the DNA in the loop, which creates the necessary hypernegatively supercoiled substrate for TOP3A to catalyze DNA relaxation.…”

Section: Synergy With Other Enzymesmentioning

confidence: 99%

“…Cells expressing defective TOP3A exhibit an increase frequency of ultra-fine anaphase bridges (UFBs) (96,113). UFBs are thin DNA structures that are stretched between the segregating sister genomes during the anaphase of mitosis (116,128,129).…”

Section: Roles Of Top3a At Ultra-fine Anaphase Bridgesmentioning

confidence: 99%

“…In addition to a possible role in resolving UFBs together with BLM, TOP3A may also act on these structures in conjunction with PICH. Indeed, PICH and TOP3A co-localize on UFBs during the anaphase of mitosis, and depletion of TOP3A or PICH inactivation leads to an increased frequency of the ultrafine anaphase bridges that arise from centromeres (Cen-UFBs) (96,132). These are the only UFBs frequently observed during an unperturbed cell cycle and are therefore believed to represent physiological structures (128).…”

Section: Roles Of Top3a At Ultra-fine Anaphase Bridgesmentioning

confidence: 99%

“…They most likely correspond to fully catenated sister chromatids that are resolved shortly after anaphase onset (134). Although efficient resolution of cen-UFBs is mediated primarily by TOP2A, it is facilitated by PICH and TOP3A (96,132). Since the decatenation activity of TOP2 has been proposed to be most efficient on positively supercoiled catenanes, there is the intriguing possibility that PICH and TOP3A catalyze positive supercoiling in order to facilitate the rapid decatenation of cen-UFBs through stimulation of TOP2A (135)(136)(137).…”

Section: Roles Of Top3a At Ultra-fine Anaphase Bridgesmentioning

confidence: 99%

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The many lives of type IA topoisomerases

Bizard

Hickson

2020

Journal of Biological Chemistry

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The double helical structure of genomic DNA is both elegant and functional in that it serves both to protect vulnerable DNA bases and to facilitate DNA replication and compaction. However, these design advantages come at the cost of having to evolve and maintain a cellular machinery that can manipulate a long polymeric molecule that readily becomes topologically entangled whenever it has to open for translation, replication, or repair. If such a machinery fails to eliminate detrimental topological entanglements, utilization of the information stored in the DNA double helix is compromised. As a consequence, the use of Bform DNA as the carrier of genetic information must have co-evolved with a means to manipulate its complex topology. This duty is performed by DNA topoisomerases, which therefore are, unsurprisingly, ubiquitous in all kingdoms of life. In this review, we focus on how DNA topoisomerases catalyze their impressive range of DNA-conjuring tricks, with a particular emphasis on DNA topoisomerase III (TOP3). Once thought to be the most unremarkable of topoisomerases, the many lives of these type IA topoisomerases are now being progressively revealed. This research interest is driven by a realization that their substrate versatility and their ability to engage in intimate collaborations with translocases and other DNA-processing enzymes are far more extensive and impressive than was thought hitherto. This, coupled with the recent associations of TOP3s with developmental and neurological pathologies in humans, is clearly making us reconsider their undeserved reputation as being unexceptional enzymes.

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Section: Synergy With Other Enzymesmentioning

confidence: 99%

Section: Roles Of Top3a At Ultra-fine Anaphase Bridgesmentioning

confidence: 99%

Section: Roles Of Top3a At Ultra-fine Anaphase Bridgesmentioning

confidence: 99%

Section: Roles Of Top3a At Ultra-fine Anaphase Bridgesmentioning

confidence: 99%

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The many lives of type IA topoisomerases

Bizard

Hickson

2020

Journal of Biological Chemistry

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“…The surface was dried under a stream of nitrogen gas, then examined by atomic force microscopy. This method is also used for studying DNA 28 . 370…”

Section: Wet-dry Cycles On Glass Substratesmentioning

confidence: 99%

Viroid-sized rings self-assemble from mononucleotides through wet-dry cycling: implications for the origin of life

Hassenkam

Damer

Mednick

et al. 2020

Preprint

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It is possible that early life relied on RNA polymers that served as ribozyme-like catalysts and store genetic information 1,2 . The source of such polymers is uncertain, but previous investigations reported that wet-dry cycles simulating prebiotic hot 20 springs provide sufficient energy to drive condensation reactions of mononucleotides to form oligomers 3 . The aim of the study reported here was to visualize the products by atomic force microscopy. In addition to globular oligomers, ring-like structures ranging from 10-200 nm in diameter with an average around 30-40 nm were abundant, particularly when nucleotides capable of base pairing were present. The 25 thickness of the rings was consistent with single stranded products, but some had thicknesses indicating base pair stacking. Others had more complex structures in the form of short polymer attachments and pairing of rings. These observations suggest the possibility that template-directed synthesis may occur during wet-dry cycling followed by solvation of the rings. We conclude that RNA-like rings and structures 30 could have been synthesized non-enzymatically on the prebiotic Earth with sizes sufficient to fold into ribozymes and genetic molecules required for life to begin.

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PICH Supports Embryonic Hematopoiesis by Suppressing a cGAS‐STING‐Mediated Interferon Response

Geng

Zhang

et al. 2022

Advanced Science

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The Plk1‐interacting checkpoint helicase (PICH) protein localizes to ultrafine anaphase DNA bridges in mitosis along with a complex of DNA repair proteins. Previous studies show PICH deficiency‐induced embryonic lethality in mice. However, the function of PICH that is required to suppress embryonic lethality in PICH‐deficient mammals remains to be determined. Previous clinical studies suggest a link between PICH deficiency and the onset of acquired aplastic anemia. Here, using Pich knock‐out (KO) mouse models, the authors provide evidence for a mechanistic link between PICH deficiency and defective hematopoiesis. Fetal livers from Pich‐KO embryos exhibit a significantly elevated number of hematopoietic stem cells (HSCs); however, these HSCs display a higher level of apoptosis and a much‐reduced ability to reconstitute a functional hematopoietic system when transplanted into lethally irradiated recipients. Moreover, these HSCs show an elevated cytoplasmic dsDNA expression and an activation of the cGAS‐STING pathway, resulting in excessive production of type I interferons (IFN). Importantly, deletion of Ifnar1 or cGAS reverses the defective hematopoiesis. The authors conclude that loss of PICH results in defective hematopoiesis via cGAS‐STING‐mediated type I IFN production.

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PICH and TOP3A cooperate to induce positive DNA supercoiling

Cited by 35 publications

References 42 publications

The many lives of type IA topoisomerases

The many lives of type IA topoisomerases

Viroid-sized rings self-assemble from mononucleotides through wet-dry cycling: implications for the origin of life

PICH Supports Embryonic Hematopoiesis by Suppressing a cGAS‐STING‐Mediated Interferon Response

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