Inner centromere localization of the CPC maintains centromere cohesion and allows mitotic checkpoint silencing

Hengeveld, Rutger C C; Vromans, Martijn J.M.; Vleugel, Mathijs; Hadders, Michael A.; Lens, Susanne M.A.

doi:10.1038/ncomms15542

Cited by 66 publications

(87 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent work has demonstrated that non-centromeric CPC results in weakened centromeric cohesion in human cells (Hengeveld et al, 2017), in accordance with previous reports that the CPC regulates centromeric cohesion (Marston, 2015). Interestingly, studies in budding yeast have shown that the inner kinetochore enriches centromeric cohesion by recruiting the cohesin loader complex (Fernius et al, 2013).…”

Section: Discussionsupporting

confidence: 89%

Distinct Roles of the Chromosomal Passenger Complex in the Detection of and Response to Errors in Kinetochore-Microtubule Attachment

et al. 2017

View full text Add to dashboard Cite

Summary The Chromosomal Passenger Complex (CPC) localizes to centromeres in early mitosis to activate its subunit Aurora B kinase. However, it is unclear if centromeric CPC localization contributes to CPC functions beyond Aurora B activation. Here, we show that an activated CPC that cannot localize to centromeres supports functional assembly of the outer kinetochore, but is unable to correct errors in kinetochore-microtubule attachment in Xenopus egg extracts. We find that CPC has two distinct roles at centromeres: one to properly phosphorylate Ndc80 to regulate attachment, and a second, conserved kinase-independent role in the proper composition of inner kinetochore proteins. Although a fully assembled inner kinetochore is not required for outer kinetochore assembly, we find it is essential to recruit tension indicators, such as BubR1 and 3F3/2, to erroneous attachments. Thus, centromeric CPC is necessary for tension-dependent removal of erroneous attachments, and for the kinetochore composition required to detect tension loss.

show abstract

Section: Discussionsupporting

confidence: 89%

Distinct Roles of the Chromosomal Passenger Complex in the Detection of and Response to Errors in Kinetochore-Microtubule Attachment

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In metaphase cells, where centromeres are stretched, the tethered HP1a split into two peaks that tracked the separating kinetochores, while untethered EY-HP1a remained as a single, somewhat broader, peak in the inner centromere ( Fig EV1B). The tethered CB-EY-HP1a remained 0.2-0.3 lm internal to the peak of CENP-C, suggesting that it occupies a kinetochore-proximal domain, as previously described for CB-INCENP (Liu et al, 2009;Wang et al, 2011;Hengeveld et al, 2017).…”

Section: Resultssupporting

confidence: 76%

HP 1α targets the chromosomal passenger complex for activation at heterochromatin before mitotic entry

et al. 2018

View full text Add to dashboard Cite

The chromosomal passenger complex (CPC) is directed to centromeres during mitosis via binding to H3T3ph and Sgo1. Whether and how heterochromatin protein 1α (HP1α) influences CPC localisation and function during mitotic entry is less clear. Here, we alter HP1α dynamics by fusing it to a CENP‐B DNA‐binding domain. Tethered HP1 strongly recruits the CPC, destabilising kinetochore–microtubule interactions and activating the spindle assembly checkpoint. During mitotic exit, the tethered HP1 traps active CPC at centromeres. These HP1‐CPC clusters remain catalytically active throughout the subsequent cell cycle. We also detect interactions between endogenous HP1 and the CPC during G2. HP1α and HP1γ cooperate to recruit the CPC to active foci in a CDK1‐independent process. Live cell tracking with Fab fragments reveals that H3S10ph appears well before H3T3 is phosphorylated by Haspin kinase. Our results suggest that HP1 may concentrate and activate the CPC at centromeric heterochromatin in G2 before Aurora B‐mediated phosphorylation of H3S10 releases HP1 from chromatin and allows pathways dependent on H3T3ph and Sgo1 to redirect the CPC to mitotic centromeres.

show abstract

“…Ipl1, Sli15, Bir1 and COMA are conserved from yeast to vertebrates and their vertebrate counterparts are called Aurora B, INCENP, Survivin and CENP-O/P/Q/U, respectively [13,38]. Crucially, it was recently reported that INCENP lacking its Survivin-binding domain (N-terminus) still supports bi-orientation in human cells [39], as does yeast Sli15 lacking its N-terminus [14]. If mechanisms are conserved between yeast and vertebrate cells, CENP-O/P/Q/R would promote recruitment of Aurora B-INCENP to inner kinetochores independently of Survivin to support error correction in vertebrate cells.…”

Section: Discussionmentioning

confidence: 99%

Aurora B-INCENP localization at centromeres/inner kinetochores is essential for chromosome bi-orientation in budding yeast

García-Rodríguez

Kasciukovic

Denninger

et al. 2019

Preprint

View full text Add to dashboard Cite

To promote chromosome bi-orientation, Aurora B kinase weakens and disrupts aberrant kinetochore-MT interaction. It has long been debated how Aurora B halts this action when biorientation is established and tension is applied across sister kinetochores. Pertinent to this debate, it was shown that Bir1 (yeast Survivin), which recruits Ipl1-Sli15 (yeast Aurora B-INCENP) to centromeres, is dispensable for bi-orientation, raising the possibility that Aurora B localization at centromeres is not required for bi-orientation. Here, we show that the COMA inner kinetochore sub-complex physically interacts with Sli15, recruits Ipl1-Sli15 to the inner kinetochore and promotes chromosome bi-orientation, independently of Bir1, in budding yeast. Moreover, using an engineered recruitment of Ipl1-Sli15 to the inner kinetochore when both Bir1 and COMA are defective, we show that localization of Ipl1-Sli15 at centromeres/ inner kinetochores is essential for bi-orientation, refuting the above possibility. Our results give important insight into how Aurora B disrupts kinetochore-MT interaction in a tensiondependent manner, to promote chromosome bi-orientation. (164 words)

show abstract

Inner centromere localization of the CPC maintains centromere cohesion and allows mitotic checkpoint silencing

Cited by 66 publications

References 63 publications

Distinct Roles of the Chromosomal Passenger Complex in the Detection of and Response to Errors in Kinetochore-Microtubule Attachment

Distinct Roles of the Chromosomal Passenger Complex in the Detection of and Response to Errors in Kinetochore-Microtubule Attachment

HP 1α targets the chromosomal passenger complex for activation at heterochromatin before mitotic entry

Aurora B-INCENP localization at centromeres/inner kinetochores is essential for chromosome bi-orientation in budding yeast

Contact Info

Product

Resources

About