The Cdt1 protein is required to license DNA for replication in fission yeast

Nishitani, Hideo; Lygerou, Zoi; Nishimoto, Tetsuya; Nurse, Paul

doi:10.1038/35007110

Cited by 436 publications

(418 citation statements)

References 25 publications

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“…8 CDT1 cooperates with CDK6 (cell division cycle 6 homolog) to promote loading of the minichromosome maintenance complex onto chromatin to form the pre-replication complex needed to initiate DNA replication. 24 …”

Section: New Loci Associated With Rbc Traits In Individuals Of Europementioning

confidence: 99%

Genetic Loci Implicated in Erythroid Differentiation and Cell Cycle Regulation Are Associated With Red Blood Cell Traits

Ding

Shameer

Jouni

et al. 2012

Mayo Clinic Proceedings

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Objective: To identify common genetic variants influencing red blood cell (RBC) traits. Patients and Methods: We performed a genomewide association study from June 2008 through July 2011 of hemoglobin, hematocrit, RBC count, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration in 12,486 patients of European ancestry from the electronic MEdical Records and Genomics (eMERGE) network. We developed an electronic medical record-based algorithm that included individuals who had RBC measurements obtained for clinical care and excluded values measured in the setting of hematopoietic disorders, comorbid conditions, or medications known to affect RBC production or a recent history of blood loss. Results: We identified 4 new genetic loci and replicated 11 loci previously reported to be associated with one or more RBC traits in individuals of European ancestry. Notably, genes present in 3 of the 4 newly identified loci (THRB, PTPLAD1, CDT1) and in 6 of the 11 replicated loci (KLF1, ALDH8A1, CCND3, SPTA1, FBXO7, TFR2/EPO) are implicated in erythroid differentiation and regulation of cell cycle in hematopoietic stem cells. Conclusion: Genes in the erythroid differentiation and cell cycle regulation pathways influence interindividual variation in RBC indices. Our results provide insights into the molecular basis underlying variation in RBC traits.

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Section: New Loci Associated With Rbc Traits In Individuals Of Europementioning

confidence: 99%

Genetic Loci Implicated in Erythroid Differentiation and Cell Cycle Regulation Are Associated With Red Blood Cell Traits

Ding

Shameer

Jouni

et al. 2012

Mayo Clinic Proceedings

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show abstract

“…(40)(41)(42)(43)(44)(45)(46) Cdt1 physically associates with Cdc6 (41) suggesting that it also forms part of the pre-RC. In Xenopus egg extracts, Cdt1 is required for licensing chromatin in vitro.…”

Section: Introductionmentioning

confidence: 99%

Perpetuating the double helix: molecular machines at eukaryotic DNA replication origins

2003

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SummaryThe hardest part of replicating a genome is the beginning. The first step of DNA replication (called ''initiation'') mobilizes a large number of specialized proteins (''initiators'') that recognize specific sequences or structural motifs in the DNA, unwind the double helix, protect the exposed ssDNA, and recruit the enzymatic activities required for DNA synthesis, such as helicases, primases and polymerases. All of these components are orderly assembled before the first nucleotide can be incorporated. On the occasion of the 50th anniversary of the discovery of the DNA structure, we review our current knowledge of the molecular mechanisms that control initiation of DNA replication in eukaryotic cells, with particular emphasis on the recent identification of novel initiator proteins. We speculate how these initiators assemble molecular machines capable of performing specific biochemical tasks, such as loading a ringshaped helicase onto the DNA double helix.

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“…The pre-replication complex forms at origins of DNA replication and is essential to initiate genome replication. 22,23 The complex consists of the origin recognition complex (encompassing the subunits ORC1 to ORC6), two regulatory proteins (CDC6 and CDT1), and the putative helicase complex (minichromosome maintenance (MCM) proteins). The origin recognition complex is loaded onto the chromatin during M and G1 phases.…”

mentioning

confidence: 99%

Meier–Gorlin syndrome genotype–phenotype studies: 35 individuals with pre-replication complex gene mutations and 10 without molecular diagnosis

et al. 2012

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Meier-Gorlin syndrome (MGS) is an autosomal recessive disorder characterized by microtia, patellar aplasia/hypoplasia, and short stature. Recently, mutations in five genes from the pre-replication complex (ORC1, ORC4, ORC6, CDT1, and CDC6), crucial in cell-cycle progression and growth, were identified in individuals with MGS. Here, we report on genotype-phenotype studies in 45 individuals with MGS (27 females, 18 males; age 3 months-47 years). Thirty-five individuals had biallelic mutations in one of the five causative pre-replication genes. No homozygous or compound heterozygous null mutations were detected. In 10 individuals, no definitive molecular diagnosis was made. The triad of microtia, absent/hypoplastic patellae, and short stature was observed in 82% of individuals with MGS. Additional frequent clinical features were mammary hypoplasia (100%) and abnormal genitalia (42%; predominantly cryptorchidism and hypoplastic labia minora/majora). One individual with ORC1 mutations only had short stature, emphasizing the highly variable clinical spectrum of MGS. Individuals with ORC1 mutations had significantly shorter stature and smaller head circumferences than individuals from other gene categories. Furthermore, compared with homozygous missense mutations, compound heterozygous mutations appeared to have a more severe effect on phenotype, causing more severe growth retardation in ORC4 and more frequently pulmonary emphysema in CDT1. A lethal phenotype was seen in four individuals with compound heterozygous ORC1 and CDT1 mutations. No other clear genotype-phenotype association was observed. Growth hormone and estrogen treatment may be of some benefit, respectively, to growth retardation and breast hypoplasia, though further studies in this patient group are needed. (MIM 224690) is a form of primordial dwarfism, characterized by microtia, short stature, and absent or hypoplastic patellae. Furthermore, pulmonary emphysema, feeding problems, various skeletal abnormalities, genitourinary anomalies, and mammary hypoplasia frequently accompany this autosomal recessive disorder. Characteristic facial features, which gradually change with age, are frequently described. Infants typically have a small mouth with full lips and micrognathia, whereas in adults, a high forehead and a more prominent, narrow nose with a broad nasal bridge are distinguishable.The first patient was reported by Meier in 1959. 1 Gorlin reported the second patient with a similar phenotype. 2 In total, only 53 cases have been described in the literature thus far. Recently, mutations in ORC1, a pre-replication complex member gene, were identified in 5 out of 204 individuals with microcephalic primordial dwarfism. 13 As individuals with mutations in ORC1 showed overlapping features with MGS, mutation analysis of ORC1 was performed in 33 individuals with MGS and revealed mutations in 4 individuals from three families. 13 Mutation analysis of other genes of this prereplication complex showed mutations in ORC4, ORC6, CDT1, and CDC6 in 14 individuals fro...

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The Cdt1 protein is required to license DNA for replication in fission yeast

Cited by 436 publications

References 25 publications

Genetic Loci Implicated in Erythroid Differentiation and Cell Cycle Regulation Are Associated With Red Blood Cell Traits

Genetic Loci Implicated in Erythroid Differentiation and Cell Cycle Regulation Are Associated With Red Blood Cell Traits

Perpetuating the double helix: molecular machines at eukaryotic DNA replication origins

Meier–Gorlin syndrome genotype–phenotype studies: 35 individuals with pre-replication complex gene mutations and 10 without molecular diagnosis

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