Biology Reference
In-Depth Information
cohesin is the glue that tethers centrioles—similar to sister chromatids—together and
separase, via cleavage of cohesin, is required for centriole disengagement (Schockel
et al.
2011
). In addition, this study also revealed a role of shugoshin, which is known
to prevent premature separation of newly replicated chromatids, in the protection of
centrioles against precocious disengagement (Schockel et al.
2011
). Furthermore,
both centrosome duplication and DNA replication are spatially and timely tightly
linked to the cell cycle. Activation of cell cycle regulators like cyclin-dependent
kinases (CDK) in distinct phases and distinct sites controls correct cell cycle pro-
gression as well as centrosome duplication. For instance, DNA replication and
centrosome duplication are assumed to be coupled by the activity of centrosomally
localized CDK2 at the G
1
/S-boundary (Ferguson and Maller
2010
). Similarly, entry
into mitosis is dependent on active CDK1 localized at centrosomes (Jackman et al.
2003
), which has recently been shown to be mediated by the centrosomal protein
Cep63. Hence, depletion of Cep63 in human cells leads to polyploid cells due to
mitotic skipping (Löffler et al.
2011
). Activation of CDK1 at centrosomes also
depends on other kinases, namely Polo-like kinase 1 (PLK1) and Aurora-A, both of
which are also essential for cell cycle progression and centrosome duplication (Barr
et al.
2004
; Vader and Lens
2008
). Hence, centrosomes and chromosomes are, at
least partially, orchestrated by the same proteins to avoid untimely replication and/or
separation which might lead to cells with abnormal DNA and/or centrosome content.
At the molecular level, the formation of new centrioles at the base of pre-existing
centrioles is best studied in Caenorhabditis elegans (C. elegans). Procentriole
formation is initiated by the recruitment of SPD-2 to the base of the existing centriole
where it is required for the correct localization of the kinase ZYG-1. ZYG-1 in return
recruits SAS-5, a protein which shuttles between the cytoplasm and the centrosome,
to the newly forming centriole. Upon interaction with SAS-5, a structural protein of
the central tube, SAS-6 localizes to the centriole. Following the formation of the
central tube, SAS-4, which is required for centriole MT assembly at the periphery of
the tube, is recruited to the centriole (Strnad and Gönczy
2008
). Homologs in humans
have been identified for SPD-2, ZYG-1, SAS-6, and SAS-4, termed CEP192
(Andersen et al.
2003
), PLK4 (Bettencourt-Dias et al.
2005
; Habedanck et al.
2005
),
HsSAS-6 (Leidel et al.
2005
), and CPAP/CENPJ (Hung et al.
2004
), respectively.
Due to domain homologies between SAS-5, Ana2, the Drosophila homolog of SAS-
5, and SIL/STIL, it was proposed that SIL/STIL might be the human ortholog of
SAS-5 (Stevens et al.
2010
). Indeed, most recently data have been published by
several groups demonstrating that SIL/STIL is required for centriole replication in
mammalian cells and might truly be the functional ortholog of SAS-5 in humans
(Tang et al.
2011
; Kitagawa et al.
2011
; Vulprecht et al.
2012
; Arquint et al.
2012
). In
mammals, centriole duplication is initiated by PLK4 activity at the pre-existing
centriole and is followed by sequential recruitment of SIL/STIL, HsSAS-6, CPAP,
CEP135, CEP110, and c-tubulin to form the base of the procentriole, subsequently
elongate the procentriole and to eventually nucleate MTs (Tang et al.
2011
; Kitagawa
et al.
2011
; Vulprecht et al.
2012
; Arquint et al.
2012
; Kleylein-Sohn et al.
2007
).
Recently, the PCM protein CEP152 was attributed a function in the recruitment of
