Dynamics of inner kinetochore assembly and maintenance in living cells

Hemmerich, Peter; Weidtkamp‐Peters, Stefanie; Hoischen, Christian; Schmiedeberg, Lars; Erliandri, Indri; Diekmann, Stephan

doi:10.1083/jcb.200710052

Cited by 174 publications

(227 citation statements)

References 88 publications

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“…2). In agreement with these findings, CENP-A nucleosomes are remarkably stable and turn over only upon replication by redistribution to the two sister chromatids (Régnier et al 2005;Jansen et al 2007;Hemmerich et al 2008). Such stability provides further evidence for a key role for CENP-A in the maintenance of centromere identity.…”

Section: Cenp-a: a Key Epigenetic Centromere Marksupporting

confidence: 76%

Temporal control of epigenetic centromere specification

2012

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All living organisms require accurate mechanisms to faithfully inherit their genetic material during cell division. The centromere is a unique locus on each chromosome that supports a multiprotein structure called the kinetochore. During mitosis, the kinetochore is responsible for connecting chromosomes to spindle microtubules, allowing faithful segregation of the duplicated genome. In most organisms, centromere position and function is not defined by the local DNA sequence context but rather by an epigenetic chromatinbased mechanism. Centromere protein A (CENP-A) is central to this process, as chromatin assembled from this histone H3 variant is essential for assembly of the centromere complex, as well as for its epigenetic maintenance. As a major determinant of centromere function, CENP-A assembly requires tight control, both in its specificity for the centromere and in timing of assembly. In the last few years, there have been several new insights into the molecular mechanism that allow this process to occur. We will review these here and discuss the general implications of the mechanism of cell cycle coupling of centromere inheritance.

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Section: Cenp-a: a Key Epigenetic Centromere Marksupporting

confidence: 76%

Temporal control of epigenetic centromere specification

2012

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“…Interestingly, a recent study in maize also showed that the in vitro binding of CENP-C to DNA is enhanced and stabilized by the presence of long, single-stranded RNA (12). Fluorescence recovery after photobleaching analysis of CENP-C cell-cycle dynamics revealed that although CENP-C undergoes dynamic exchange throughout most of the cell cycle, CENP-C is stably bound at the mitotic kinetochore (30). The mitotic transcripts generated by the kinetochore-associated RNAPII reported here could function to stabilize the association of CENP-C at the kinetochore during mitosis.…”

Section: Discussionmentioning

confidence: 99%

Active transcription and essential role of RNA polymerase II at the centromere during mitosis

Chan

Marshall

Saffery

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

239

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Transcription of the centromeric regions has been reported to occur in G1 and S phase in different species. Here, we investigate whether transcription also occurs and plays a functional role at the mammalian centromere during mitosis. We show the presence of actively transcribing RNA polymerase II (RNAPII) and its associated transcription factors, coupled with the production of centromere satellite transcripts at the mitotic kinetochore. Specific inhibition of RNAPII activity during mitosis leads to a decrease in centromeric α-satellite transcription and a concomitant increase in anaphase-lagging cells, with the lagging chromosomes showing reduced centromere protein C binding. These findings demonstrate an essential role of RNA-PII in the transcription of α-satellite DNA, binding of centromere protein C, and the proper functioning of the mitotic kinetochore.chromatin | noncoding RNA | epigenetics T he centromere is an essential chromosomal structure that mediates microtubule attachment during cell division to ensure correct chromosome segregation. Although centromere function is highly conserved, centromere DNA sequences show no evolutionary conservation. Instead, centromeric chromatin typically is filled with species-specific satellite DNA sequences that lack transcribed genes. The presence of functional ectopic centromeres (neocentromeres) at genomic regions devoid of classical satellite DNA repeats confirmed the epigenetic nature of centromere function (1).The centromere is organized into two broad domains characterized by distinct sets of epigenetic determinants. The centromere core domain comprises the centromere-specific histone H3 variant centromere protein A (CENP-A) that is essential for kinetochore formation, whereas the pericentric heterochromatin is vital for sister chromatid cohesion (for review, see ref.2). In yeast, pericentric outermost DNA repeats are transcribed and processed by RNAi machinery into siRNAs, which direct the deposition of heterochromatic markers such as H3K9me3 and HP1 at the pericentric heterochromatin (3). The RNAi pathway also has been shown to be vital for the establishment of pericentric heterochromatin in plant and animal cells (4, 5). However, although the depletion of Dicer in human-chicken hybrid cells causes defective pericentric heterochromatin, it does not affect the binding of CENP-A and centromere protein C (CENP-C) at the centromere core domain (6), suggesting that the RNAi pathway is not required for core centromere function. Our previous studies showed that transcription is permissible within the kinetochore domain of a human neocentromere (7, 8), but others have reported the presence of active genes within the rice kinetochore domain (9). Consistent with these reports, the CENP-A domain in Drosophila and human cells is enriched with the euchromatin-like marker H3K4me2 (10). Such studies suggest that transcription of centromeric chromatin is permissible and compatible with centromere function. Furthermore, we and others have demonstrated the presence of RNA at th...

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“…14,15 Importantly, while CENP-A nucleosomes are stably bound to centromeric chromatin, 16 the binding of CCAN proteins appears to be dynamic. [17][18][19] CENP-C and CENP-T serve as a platform for recruitment of the KMN network through pathways that are not yet well understood. [20][21][22][23][24][25][26][27][28][29] From the CCAN components, CENP-N and CENP-C recognize CENP-A.…”

Section: Introductionmentioning

confidence: 99%