The centriolar satellite protein Cep131 is important for genome stability.

Abstract

SummaryThe centrosome acts as a centre for microtubule organisation and plays crucial roles in cell polarity, migration, growth and division. Cep131 has recently been described as a basal body component essential for cilium formation, but its function in non-ciliogenic cells is unknown. We identified human Cep131 (also known as AZI1) in a screen for regulators of genome stability. We show that centrosomal localisation of Cep131 is cell-cycle-regulated and requires both an intact microtubule network and a functional dynein-dynactin transport system. Cep131 is recruited to centriolar satellites by PCM1, and localised to the centriolar core region by both pericentrin and Cep290. Depletion of Cep131 results in a reduction in proliferation rate, centriole amplification, an increased frequency of multipolar mitosis, chromosomal instability and an increase in post-mitotic DNA damage. These data therefore highlight the importance of human Cep131 for maintaining genomic integrity.

Centriolar satellite– and hMsd1/SSX2IP-dependent microtubule anchoring is critical for centriole assembly

“…In line with this notion, PCM1 particles still localize around the centrosome after the depletion of several satellite components (Staples et al ., 2012; Lee and Stearns, 2013). The depletion of certain other components alternatively causes the distribution pattern of PCM1 to become more dispersed (Lopes et al ., 2011; Kim and Rhee, 2012).…”

“…Recent studies show that in addition to hMsd1/SSX2IP, multiple molecules and pathways are involved in the suppression of supernumerary centriole formation. These include Cep76 (Tsang et al ., 2009), LGALS3BP (Fogeron et al ., 2013), Cep131/Azi1 (Staples et al ., 2012), and CCDC14 (Firat-Karalar et al ., 2014). Of interest, the depletion of these molecules has a variety of effects in nontransformed and cancer cells, often varying within specific lines (Staples et al ., 2012; Fogeron et al ., 2013).…”

“…Cancer cells are likely to endure defective centriole duplication, possibly by exploiting alternate pathways. Among molecules exerting inhibitory roles in centriole amplification, Cep131/Azi1 and CCDC14 are components of centriolar satellites (Staples et al ., 2012; Firat-Karalar et al ., 2014). Functional relationships between these two molecules and hMsd1/SSX2IP need to be addressed in the future.…”

MRNIP/C5orf45 Interacts with the MRN Complex and Contributes to the DNA Damage Response

“…We recently carried out a genome-wide small interfering RNA (siRNA) screen in HCT116 colorectal carcinoma-derived cells to identify previously uncharacterized regulators of genome stability, using phosphorylation of the histone variant H2AX on Ser139 (γH2AX) as a marker of increased DNA damage (Staples et al., 2012, Staples et al., 2014). From this screen, we identified C5orf45, which yielded a relatively high Z score of 1.7.…”

BRCA1 and FancJ cooperatively promote interstrand crosslinker induced centrosome amplification through the activation of polo-like kinase 1

“…For example, deficiency of centrosomal proteins, such as pericentrin (PCNT), CEP131, CEP152, and CEP164, causes DDR defects. [12][13][14][15] On the other hand, deficiency of certain DDR proteins, including BRCA1, induces centrosome amplification. 16,17 Further supporting this connection, it has long been observed that a variety of genotoxic stress can induce pronounced centrosome amplification (DNA damage induced centrosome amplification, or DDICA).…”