Nap1 regulates proper CENP-B binding to nucleosomes

Tachiwana, Hiroaki; Miya, Yuta; Shono, Nobuaki; Ohzeki, Jun Ichirou; Osakabe, Akihisa; Otake, Kazuo; Larionov, Vladimir; Earnshaw, William C.; Kimurâ, Hiroshi; Masumoto, Hiroshi; Kurumizaka, Hitoshi

doi:10.1093/nar/gks1464

Cited by 18 publications

(22 citation statements)

References 68 publications

(58 reference statements)

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“…Since crystal or NMR structure of G4 DNAzyme remains unexplored, we performed molecular docking and dynamics simulation by using AutoDock and NAMD programs to understand the hemin-binding micro-environment of G4 DNAzymes (47–49). As shown in Figure 5, hemin stacks well upon the 3′-G-quartet of Dz-00 and Dz-11.…”

Section: Resultsmentioning

confidence: 99%

Insight into G-quadruplex-hemin DNAzyme/RNAzyme: adjacent adenine as the intramolecular species for remarkable enhancement of enzymatic activity

Liu

et al. 2016

Nucleic Acids Research

177

158

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G-quadruplex (G4) with stacked G-tetrads structure is able to bind hemin (iron (III)-protoporphyrin IX) to form a unique type of DNAzyme/RNAzyme with peroxidase-mimicking activity, which has been widely employed in multidisciplinary fields. However, its further applications are hampered by its relatively weak activity compared with protein enzymes. Herein, we report a unique intramolecular enhancement effect of the adjacent adenine (EnEAA) at 3′ end of G4 core sequences that significantly improves the activity of G4 DNAzymes. Through detailed investigations of the EnEAA, the added 3′ adenine was proved to accelerate the compound I formation in catalytic cycle and thus improve the G4 DNAzyme activity. EnEAA was found to be highly dependent on the unprotonated state of the N1 of adenine, substantiating that adenine might function as a general acid–base catalyst. Further adenine analogs analysis supported that both N1 and exocyclic 6-amino groups in adenine played key role in the catalysis. Moreover, we proved that EnEAA was generally applicable for various parallel G-quadruplex structures and even G4 RNAzyme. Our studies implied that adenine might act analogously as the distal histidine in protein peroxidases, which shed light on the fundamental understanding and rational design of G4 DNAzyme/RNAzyme catalysts with enhanced functions.

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Section: Resultsmentioning

confidence: 99%

Insight into G-quadruplex-hemin DNAzyme/RNAzyme: adjacent adenine as the intramolecular species for remarkable enhancement of enzymatic activity

Liu

et al. 2016

Nucleic Acids Research

177

158

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“…Interestingly, to date, 3 out of 8 cases of described pseudodicentric neocentric chromosomes in humans occur on the Y chromosome (Marshall et al, 2008) where centromere re-activation is predicted to be less frequent due to lack of CENP-B. Previous reports have suggested that CENP-B is removed from non-centromeric regions via its chaperone Nap1 (Tachiwana et al, 2013). Considering our findings, such regulation appears also to be important to prevent CENP-B-driven centromere formation outside of alpha-satellite DNA.…”

Section: Discussionmentioning

confidence: 99%

A genetic memory initiates the epigenetic loop necessary to preserve centromere position

et al. 2020

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Centromeres are built on repetitive DNA sequences (CenDNA) and a specific chromatin enriched with the histone H3 variant CENP-A, the epigenetic mark that identifies centromere position. Here, we interrogate the importance of CenDNA in centromere specification by developing a system to rapidly remove and reactivate CENP-A (CENP-A OFF/ ON). Using this system, we define the temporal cascade of events necessary to maintain centromere position. We unveil that CENP-B bound to CenDNA provides memory for maintenance on human centromeres by promoting de novo CENP-A deposition. Indeed, lack of CENP-B favors neocentromere formation under selective pressure. Occasionally, CENP-B triggers centromere re-activation initiated by CENP-C, but not CENP-A, recruitment at both ectopic and native centromeres. This is then sufficient to initiate the CENP-A-based epigenetic loop. Finally, we identify a population of CENP-A-negative, CENP-B/C-positive resting CD4 + T cells capable to re-express and reassembles CENP-A upon cell cycle entry, demonstrating the physiological importance of the genetic memory.

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“…formation of human artificial chromosomes or HACs) ( 9 , 10 ). HOR units are enriched with a 17-bp binding motif for centromere protein B (CENP-B box) that is required for de novo kinetochore formation as well as for prevention of CENP-A nucleosome assembly at ectopic chromosomal sites ( 11 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

Replication of alpha-satellite DNA arrays in endogenous human centromeric regions and in human artificial chromosome

Erliandri¹,

Fu²,

Nakano³

et al. 2014

Nucleic Acids Research

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In human chromosomes, centromeric regions comprise megabase-size arrays of 171 bp alpha-satellite DNA monomers. The large distances spanned by these arrays preclude their replication from external sites and imply that the repetitive monomers contain replication origins. However, replication within these arrays has not previously been profiled and the role of alpha-satellite DNA in initiation of DNA replication has not yet been demonstrated. Here, replication of alpha-satellite DNA in endogenous human centromeric regions and in de novo formed Human Artificial Chromosome (HAC) was analyzed. We showed that alpha-satellite monomers could function as origins of DNA replication and that replication of alphoid arrays organized into centrochromatin occurred earlier than those organized into heterochromatin. The distribution of inter-origin distances within centromeric alphoid arrays was comparable to the distribution of inter-origin distances on randomly selected non-centromeric chromosomal regions. Depletion of CENP-B, a kinetochore protein that binds directly to a 17 bp CENP-B box motif common to alpha-satellite DNA, resulted in enrichment of alpha-satellite sequences for proteins of the ORC complex, suggesting that CENP-B may have a role in regulating the replication of centromeric regions. Mapping of replication initiation sites in the HAC revealed that replication preferentially initiated in transcriptionally active regions.

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Nap1 regulates proper CENP-B binding to nucleosomes

Cited by 18 publications

References 68 publications

Insight into G-quadruplex-hemin DNAzyme/RNAzyme: adjacent adenine as the intramolecular species for remarkable enhancement of enzymatic activity

Insight into G-quadruplex-hemin DNAzyme/RNAzyme: adjacent adenine as the intramolecular species for remarkable enhancement of enzymatic activity

A genetic memory initiates the epigenetic loop necessary to preserve centromere position

Replication of alpha-satellite DNA arrays in endogenous human centromeric regions and in human artificial chromosome

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