CEP proteins: the knights of centrosome dynasty

Kumar, Ambuj; Rajendran, Vidya; Sethumadhavan, Rao; Purohit, Rituraj

doi:10.1007/s00709-013-0488-9

Cited by 83 publications

(70 citation statements)

References 114 publications

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“…CEP250 encodes the C-Nap1 protein which belongs to the CEP family of proteins,35 including over 30 proteins that form the active component of centrosome and play a vital role in centriole biogenesis, centrosome cohesion and cell cycle progression control 36. C-Nap1 dissociates from spindle poles during mitosis, but reaccumulates at centrosomes at the end of cell division and was shown to be required for cell cycle-regulated centrosome cohesion 37.…”

Section: Discussionmentioning

confidence: 99%

A homozygous nonsense CEP250 mutation combined with a heterozygous nonsense C2orf71 mutation is associated with atypical Usher syndrome

et al. 2014

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Section: Discussionmentioning

confidence: 99%

A homozygous nonsense CEP250 mutation combined with a heterozygous nonsense C2orf71 mutation is associated with atypical Usher syndrome

et al. 2014

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“…This relationship has motivated intense efforts to elaborate the composition and mechanism of action of core DNA repair machinery as well as peripheral molecular systems that modulate this machinery to suppress genomic instability (2)(3)(4)(5). With respect to the latter, emerging evidence implicates multiple regulatory layers that link activation of the DNA damage response (DDR), repair pathway choice, and resolution of the DDR to chromatin organization (6)(7)(8)(9), RNA metabolism (10,11), and autophagy (12)(13)(14).…”

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confidence: 99%

Role of the Exocyst Complex Component Sec6/8 in Genomic Stability

Torres

Pandita

Kulak

et al. 2015

Molecular and Cellular Biology

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The exocyst is a heterooctomeric complex well appreciated for its role in the dynamic assembly of specialized membrane domains. Accumulating evidence indicates that this macromolecular machine also serves as a physical platform that coordinates regulatory cascades supporting biological systems such as host defense signaling, cell fate, and energy homeostasis. The isolation of multiple components of the DNA damage response (DDR) as exocyst-interacting proteins, together with the identification of Sec8 as a suppressor of the p53 response, suggested functional interactions between the exocyst and the DDR. We found that exocyst perturbation resulted in resistance to ionizing radiation (IR) and accelerated resolution of DNA damage. This occurred at the expense of genomic integrity, as enhanced recombination frequencies correlated with the accumulation of aberrant chromatid exchanges. Sec8 perturbation resulted in the accumulation of ATF2 and RNF20 and the promiscuous accumulation of DDR-associated chromatin marks and Rad51 repairosomes. Thus, the exocyst supports DNA repair fidelity by limiting the formation of repair chromatin in the absence of DNA damage. The faithful repair of DNA damage is integral to the maintenance of the genome and suppression of oncogenesis (1). This relationship has motivated intense efforts to elaborate the composition and mechanism of action of core DNA repair machinery as well as peripheral molecular systems that modulate this machinery to suppress genomic instability (2-5). With respect to the latter, emerging evidence implicates multiple regulatory layers that link activation of the DNA damage response (DDR), repair pathway choice, and resolution of the DDR to chromatin organization (6-9), RNA metabolism (10, 11), and autophagy (12)(13)(14). By extrapolation, the coordinated response of cellular processes to DNA damage is necessary for efficient DNA repair, and perturbations of these pathways can lead to genomic instability and development of neoplastic disease.The exocyst (also known as the Sec6/8 complex) is a conserved heterooctomeric protein complex, which includes Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo84, and Exo70. The holocomplex is well appreciated for its role in the dynamic trafficking of secretory vesicles to specialized membrane domains such as the basolateral membrane of polarized epithelial cells (15) and abscission planes in dividing cells (16) and to lamellipodia and growth cones of migrating cells and differentiating neurons (17, 18). Accumulating evidence indicates that exocyst subcomplexes, and their regulation by Ras and Rho family GTPases, also selectively participate in the assembly and activation of signal transduction events that mediate host defense, autophagy, cell growth, and oncogene signaling (19-23). An overarching implication is that the exocyst and its subcomplexes serve as physical platforms that coordinate organellar assembly with the activation of attendant regulatory cascades required for the execution of distinct cell biological programs.Here, we ...

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“…For example, mutations of Cep290, known as BBS14 or KIAA0373, are observed in ciliopathies which are a group of diseases associated with ciliary dysfunction such as retinal degeneration, Joubert syndrome type 5, and Bardet-Biedl syndrome type 14 (BBS14) [11]. Cep290 is a satellite protein that localizes at the transition zone between basal body and cilia [8]. Recently, it has been reported that Cep290 plays a role in the ciliary transport process and is associated with several satellite proteins.…”

Section: Introductionmentioning

confidence: 99%

“…CEP family proteins are components of centrosome and essential for cell division. These proteins primarily control centriole duplication, MTkinetochore (KT) assembly, bipolarity, and mitotic progression [8]. Thirty-one CEP proteins have been identified and many of them are being evaluation.…”

Section: Introductionmentioning

confidence: 99%