An emerging role of transcription in chromosome segregation: Ongoing centromeric transcription maintains centromeric cohesion

Chen, Yujue; Liu, Hong

doi:10.1002/bies.202100201

Cited by 4 publications

(4 citation statements)

References 47 publications

(76 reference statements)

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“…Centromeres are highly repetitive areas of chromosomes with a fundamental role on sister chromatin segregation during mitosis. Interestingly, studies ranging from insect to vertebrate cells show retention of active transcription at these regions in mitosis [ 9 , 10 , 22 ]. The relative enrichment of transcription at centromeres might provide cells with a mechanism to allocate factors specifically at these regions and guarantee the accurate segregation of chromosomes ( Figure 2A ).…”

Section: Why Cells Selectively Repress Transcription In Mitosis?mentioning

confidence: 99%

Transcriptional repression across mitosis: mechanisms and functions

Contreras,

Perea-Resa

2024

Biochemical Society Transactions

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Transcription represents a central aspect of gene expression with RNA polymerase machineries (RNA Pol) driving the synthesis of RNA from DNA template molecules. In eukaryotes, a total of three RNA Pol enzymes generate the plethora of RNA species and RNA Pol II is the one transcribing all protein-coding genes. A high number of cis- and trans-acting factors orchestrates RNA Pol II-mediated transcription by influencing the chromatin recruitment, activation, elongation, and/or termination steps. The levels of DNA accessibility, defining open-euchromatin versus close-heterochromatin, delimits RNA Pol II activity as well as the encounter with other factors acting on chromatin such as the DNA replication or DNA repair machineries. The stage of the cell cycle highly influences RNA Pol II activity with mitosis representing the major challenge. In fact, there is a massive inhibition of transcription during the mitotic entry coupled with chromatin dissociation of most of the components of the transcriptional machinery. Mitosis, as a consequence, highly compromises the transcriptional memory and the perpetuation of cellular identity. Once mitosis ends, transcription levels immediately recover to define the cell fate and to safeguard the proper progression of daughter cells through the cell cycle. In this review, we evaluate our current understanding of the transcriptional repression associated with mitosis with a special focus on the molecular mechanisms involved, on the potential function behind the general repression, and on the transmission of the transcriptional machinery into the daughter cells. We finally discuss the contribution that errors in the inheritance of the transcriptional machinery across mitosis might play in stem cell aging.

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Section: Why Cells Selectively Repress Transcription In Mitosis?mentioning

confidence: 99%

Transcriptional repression across mitosis: mechanisms and functions

Contreras,

Perea-Resa

2024

Biochemical Society Transactions

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“…Satellite DNAs, one of the most divergent non-coding regions on a chromatin across eukaryotes 3 , had once been thought to be transcriptionally inert but are now known to undergo active transcription catalyzed by RNA Polymerase (RNAP) II 4,5 . The RNAP II-dependent satellite transcription promotes centromere function by maintaining centromere identity across eukaryotes 6–13 and centromeric cohesion in human cells 14–17 . Both ongoing transcriptional process per se and transcribed non-coding satellite RNAs seem to be involved.…”

Section: Introductionmentioning

confidence: 99%

“…However, the intrinsic and external responsive regulations of satellite transcription are little understood, especially in higher organisms including human, in which the centromere typically forms at hundreds to thousands of α-satellite DNA repeats 18 , which are further assembled into high-order repeats (HORs). This could be partially due to lack of accurate and complete centromere sequencing and assembly 17 . Fortunately, the most recent advance in complete human genome sequencing and assembly offers a grant opportunity for us to better understand the role and regulation of α-satellite transcription 19–21 .…”

Section: Introductionmentioning

confidence: 99%

Topoisomerase I is an Evolutionarily Conserved Key Regulator for Satellite DNA Transcription

Teng,

Yang,

Zhang

et al. 2024

Preprint

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Repetitive satellite DNAs, divergent in nucleic-acid sequence and size across eukaryotes, provide a physical site for centromere assembly to orchestrate chromosome segregation during the cell cycle. These non-coding DNAs are transcribed by RNA polymerase (RNAP) II and the transcription has been shown to play a role in chromosome segregation, but a little is known about the regulation of centromeric transcription, especially in higher organisms with tandemly-repeated-DNA-sequence centromeres. Using RNA interference knockdown, chemical inhibition and AID/IAA degradation, we show that Topoisomerase I (TopI), not TopII, promotes the transcription of α-satellite DNAs, the main type of satellite on centromeres in human cells. Mechanistically, TopI localizes to centromeres, binds RNAP II and facilitates RNAP II elongation on centromeres. Interestingly, in response to DNA double-stranded breaks (DSBs) induced by chemotherapy drugs or CRSPR/Cas9, α-satellite transcription is dramatically stimulated in a DNA damage checkpoint-independent but TopI-dependent manner. These DSB-induced α-satellite RNAs were predominantly derived from the α-satellite high-order repeats of human centromeres and forms into strong speckles in the nucleus. Remarkably, TopI-dependent satellite transcription also exists in mouse 3T3 and Drosophila S2 cells and in Drosophila larval imaginal wing discs and tumor tissues. Altogether, our findings herein reveal an evolutionally conserved mechanism with TopI as a key player for the regulation of satellite transcription at both cellular and animal levels.

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“…However, recent many studies have demonstrated that transcription into non-coding RNA (ncRNA) occurs at the centromeres although the centromeric transcription levels are low (2)(3)(4)(5)(6). Centromeric transcription and its ncRNA products have been shown to play crucial roles in centromere functions and kinetochore assembly (7)(8)(9)(10). However, there is limited understanding regarding molecular properties of centromeric ncRNA, including nucleotide sequences and transcription regulation.…”

Section: Introductionmentioning

confidence: 99%