Condensin Depletion Causes Genome Decompaction Without Altering the Level of Global Gene Expression in<i>Saccharomyces cerevisiae</i>

Paul, Matthew R.; Markowitz, Tovah E.; Hochwagen, Andreas; Ercan, Sevinç

doi:10.1534/genetics.118.301217

Cited by 33 publications

(46 citation statements)

References 89 publications

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“…We depleted condensin subunit Brn1 from the nucleus to determine whether the role of condensin in DNA compaction impedes replication-fork progression at tDNAs. The Brn1-FRB construct has previously been described, and rapamycin treatment of this strain leads to dramatic loss of higherorder chromosome structure consistent with substantial loss of condensin binding (Paul et al 2018).…”

Section: Loss Of Condensin (Brn1) Binding Has No Effect On Replisome mentioning

confidence: 72%

“…Fork progression did not change at the subset of tDNAs that lose interchromosomal interactions upon Brn1 depletion (Fig. S2) (Paul et al 2018). Since a global loss of condensin binding and interchromosomal interactions does not rescue fork progression, we conclude that neither condensin itself, nor the long-range chromosomal interactions it facilitates, present a significant obstacle to replisome passage at tDNAs in rrm3Δ.…”

Section: Loss Of Condensin (Brn1) Binding Has No Effect On Replisome mentioning

confidence: 86%

“…The association of condensin at these sites is downstream of TFIIIC recruitment and mediates the clustering of condensin-associated tDNAs (Haeusler et al 2008). tDNA clustering is lost along with other intra-and interchromosomal interactions upon condensin depletion (Paul et al 2018), but this destruction of chromosome architecture does not increase the likelihood of replisome passage at tDNAs (Fig. 3).…”

Section: Replisome Progression Through a Structured Chromatin Environmentioning

confidence: 99%

“…Figure S2: Loss of tDNA-tDNA interactions via Brn1 depletion has no effect on replisome progression at tDNAs. Replisome direction around tDNAs transcribed in either direction, >5kb away from the closest origin, that lost homotypic interchromosomal interactions after Brn1 depletion (n=25) (Paul et al, 2018). WT: Dox-repressible CDC9 strain congenic with rrm3∆.…”

Section: Accessory Factors That Enhance Replication-fork Stalling At mentioning

confidence: 99%

“…By FISH, tDNAs are sequestered in the nucleolus throughout the cell cycle, dependent on interactions between condensin subunits Smc2 and Smc4, TFIIIB subunit Brf1 and TFIIIC subunit Tfc1 (Haeusler et al 2008). Depletion of the condensin subunit Brn1 leads to a decrease in intrachromosomal interactions genome-wide, and a loss of interchromosomal homotypic interactions at a subset of tDNAs (Paul et al 2018). Apart from tDNAs, condensin is also enriched at centromeres and rDNA genes (Wang et al 2016;Lazar-Stefanita et al 2017;Schalbetter et al 2017).…”

Section: Introductionmentioning

confidence: 99%

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The impediment to replication at tRNA genes inS. cerevisiaedoes not require tRNA transcription, and is facilitated by topoisomerases and Rad18-dependent repair pathways

Yeung

Smith

2020

Preprint

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tRNA genes are widely studied sites of replication-fork pausing and genome instability in the budding yeast Saccharomyces cerevisiae. tRNAs are extremely highly transcribed and serve as constitutive condensin binding sites. tRNA transcription by RNA polymerase III has previously been identified as stimulating replication-fork pausing at tRNA genes, but the nature of the block to replication has not been incontrovertibly demonstrated. Here, we describe a systematic, genome-wide analysis of the contributions of candidates to replication-fork progression at tDNAs in yeast: transcription factor binding, transcription, topoisomerase activity, condensin-mediated clustering, and Rad18-dependent DNA repair. We show that an asymmetric block to replication is maintained even when tRNA transcription is abolished by depletion of one or more subunits of RNA polymerase III. By contrast, analogous depletion of the essential transcription factor TFIIIB removes the obstacle to replication.Therefore, our data suggest that the RNA polymerase III transcription complex itself represents an asymmetric obstacle to replication even in the absence of RNA synthesis. We additionally demonstrate that replication-fork progression past tRNA genes is unaffected by the global depletion of condensin from the nucleus, and can be stimulated by the removal of topoisomerases or Rad18dependent DNA repair pathways. genome instability at these sites are mitigated by the redundant activity of the Pif1-family helicases Pif1 and Rrm3 (Osmundson et al. 2017;Tran et al. 2017). Consistent with head-on replicationtranscription conflicts at tDNAs being deleterious, tDNAs show a strong bias towards the codirectional orientation in the yeast genome (Osmundson et al. 2017). An analogous statistical coorientation of replication and transcription is not observed for protein-coding genes in yeast (Raghuraman et al. 2001) but is prevalent in prokaryotes (Rocha and Danchin 2003) and has been described for both the C. elegans (Pourkarimi et al. 2016) and human replication programs (Petryk et al. 2016; Chen et al. 2019). Thus, replication-transcription conflicts can shape genome architecture and replication dynamics across biological kingdoms. Replication-transcription conflicts at both tDNAs and protein-coding genes are associated with genome instability in yeast (Prado and Aguilera 2005; Tran et al. 2017). Interestingly, replisome pausing and the onset of DNA damage at tDNAs appear to be mechanistically separable: co-oriented collisions in the absence of both Pif1 helicases impede a substantial fraction of replisomes (Osmundson et al. 2017; Tran et al. 2017), but only head-on conflicts lead to a dramatic increase in Rloop-dependent gross chromosomal rearrangements (Tran et al. 2017). Similarly to tDNAs, transcription-dependent mitotic recombination is strongly biased to the head-on orientation at a model protein-coding gene in yeast (Prado and Aguilera 2005). In humans, codirectional and head-on conflicts with RNA polymerase II both impede the replisome, but elicit di...

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Section: Loss Of Condensin (Brn1) Binding Has No Effect On Replisome mentioning

confidence: 72%

Section: Loss Of Condensin (Brn1) Binding Has No Effect On Replisome mentioning

confidence: 86%

Section: Replisome Progression Through a Structured Chromatin Environmentioning

confidence: 99%

Section: Accessory Factors That Enhance Replication-fork Stalling At mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The impediment to replication at tRNA genes inS. cerevisiaedoes not require tRNA transcription, and is facilitated by topoisomerases and Rad18-dependent repair pathways

Yeung

Smith

2020

Preprint

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Keeping intracellular DNA untangled: A new role for condensin?

et al. 2021

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The DNA‐passage activity of topoisomerase II accidentally produces DNA knots and interlinks within and between chromatin fibers. Fortunately, these unwanted DNA entanglements are actively removed by some mechanism. Here we present an outline on DNA knot formation and discuss recent studies that have investigated how intracellular DNA knots are removed. First, although topoisomerase II is able to minimize DNA entanglements in vitro to below equilibrium values, it is unclear whether such capacity performs equally in vivo in chromatinized DNA. Second, DNA supercoiling could bias topoisomerase II to untangle the DNA. However, experimental evidence indicates that transcriptional supercoiling of intracellular DNA boosts knot formation. Last, cohesin and condensin could tighten DNA entanglements via DNA loop extrusion (LE) and force their dissolution by topoisomerase II. Recent observations indicate that condensin activity promotes the removal of DNA knots during interphase and mitosis. This activity might facilitate the spatial organization and dynamics of chromatin.

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Condensin action and compaction

2018

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Condensin is a multi-subunit protein complex that belongs to the family of structural maintenance of chromosomes (SMC) complexes. Condensins regulate chromosome structure in a wide range of processes including chromosome segregation, gene regulation, DNA repair and recombination.Recent research defined the structural features and molecular activities of condensins, but it is unclear how these activities are connected to the multitude of phenotypes and functions attributed to condensins. In this review, we briefly discuss the different molecular mechanisms by which condensins may regulate global chromosome compaction, organization of topologically associated domains, clustering of specific loci such as tRNA genes, rDNA segregation, and gene regulation.

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Condensin Depletion Causes Genome Decompaction Without Altering the Level of Global Gene Expression inSaccharomyces cerevisiae

Cited by 33 publications

References 89 publications

The impediment to replication at tRNA genes inS. cerevisiaedoes not require tRNA transcription, and is facilitated by topoisomerases and Rad18-dependent repair pathways

The impediment to replication at tRNA genes inS. cerevisiaedoes not require tRNA transcription, and is facilitated by topoisomerases and Rad18-dependent repair pathways

Keeping intracellular DNA untangled: A new role for condensin?

Condensin action and compaction

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