Mitotic chromosome condensation in the rDNA requires TRF4 and DNA topoisomerase I in Saccharomyces cerevisiae.

Castaño, Irene; Brzoska, Pius; Sadoff, Ben U.; Chen, H; Christman, Michael F.

doi:10.1101/gad.10.20.2564

Cited by 112 publications

(86 citation statements)

References 49 publications

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“…Condensation defect was also detected in a double mutant trf4 top1 (Castano et al, 1996). TRF4 was identified in a screen for mutations that are inviable in combination with topoisomerase I null mutation.…”

Section: Introductionmentioning

confidence: 99%

Chromosome Condensation Factor Brn1p Is Required for Chromatid Separation in Mitosis

Ouspenski

Cabello

Brinkley

2000

MBoC

100

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This work describes BRN1, the budding yeast homologue of Drosophila Barren and Xenopus condensin subunit XCAP-H. The Drosophila protein is required for proper chromosome segregation in mitosis, and Xenopus protein functions in mitotic chromosome condensation. Mutant brn1 cells show a defect in mitotic chromosome condensation and sister chromatid separation and segregation in anaphase. Chromatid cohesion before anaphase is properly maintained in the mutants. Some brn1 mutant cells apparently arrest in S-phase, pointing to a possible function for Brn1p at this stage of the cell cycle. Brn1p is a nuclear protein with a nonuniform distribution pattern, and its level is up-regulated at mitosis. Temperature-sensitive mutations of BRN1 can be suppressed by overexpression of a novel gene YCG1, which is homologous to another Xenopus condensin subunit, XCAP-G. Overexpression of SMC2, a gene necessary for chromosome condensation, and a homologue of the XCAP-E condensin, does not suppress brn1, pointing to functional specialization of components of the condensin complex.

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Section: Introductionmentioning

confidence: 99%

Chromosome Condensation Factor Brn1p Is Required for Chromatid Separation in Mitosis

Ouspenski

Cabello

Brinkley

2000

MBoC

100

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“…TRF5 is a homolog of TRF4, and deletion of both genes is lethal, indicating that their functions are overlapping and essential for cell viability (5). A role for TRF4 in chromosome condensation is indicated from the observation that a top1 trf4 ts double mutant fails to establish and maintain chromosome condensation in rRNA genes at mitosis (4). Furthermore, the Trf4 protein interacts physically with the Smc1 and Smc2 proteins that bind chromosomes and cause condensation (4).…”

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confidence: 99%

Trf4 and Trf5 Proteins of Saccharomyces cerevisiae Exhibit Poly(A) RNA Polymerase Activity but No DNA Polymerase Activity

Haracska

Johnson

Prakash

et al. 2005

Molecular and Cellular Biology

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The Saccharomyces cerevisiae Trf4 and Trf5 proteins are members of a distinct family of eukaryotic DNA polymerase ␤-like nucleotidyltransferases, and a template-dependent DNA polymerase activity has been reported for Trf4. To define the nucleotidyltransferase activities associated with Trf4 and Tr5, we purified these proteins from yeast cells and show that whereas both proteins exhibit a robust poly(A) polymerase activity, neither of them shows any evidence of a DNA polymerase activity. The poly(A) polymerase activity, as determined for Trf4, is strictly Mn 2؉ dependent and highly ATP specific, incorporating AMP onto the free 3-hydroxyl end of an RNA primer. Unlike the related poly(A) polymerases from other eukaryotes, which are located in the cytoplasm and regulate the stability and translation efficiency of specific mRNAs, the Trf4 and Trf5 proteins are nuclear, and a multiprotein complex associated with Trf4 has been recently shown to polyadenylate a variety of misfolded or inappropriately expressed RNAs which activate their degradation by the exosome. To account for the effects of Trf4/Trf5 proteins on the various aspects of DNA metabolism, including chromosome condensation, DNA replication, and sister chromatid cohesion, we suggest an additional and essential role for the Trf4 and Trf5 protein complexes in generating functional mRNA poly(A) tails in the nucleus.The TRF4 gene of Saccharomyces cerevisiae was first identified in a genetic screen for mutations that are synthetically lethal with mutations in DNA topoisomerase I (20). TRF5 is a homolog of TRF4, and deletion of both genes is lethal, indicating that their functions are overlapping and essential for cell viability (5). A role for TRF4 in chromosome condensation is indicated from the observation that a top1 trf4 ts double mutant fails to establish and maintain chromosome condensation in rRNA genes at mitosis (4). Furthermore, the Trf4 protein interacts physically with the Smc1 and Smc2 proteins that bind chromosomes and cause condensation (4). TRF4 and TRF5 have also been suggested to have an essential role in the coordination between DNA replication and sister chromatid cohesion (25). In another study, the deletion of TRF4 alone was found to have no effect on sister chromatid cohesion in mitotic metaphase cells or on chromosome segregation during meiosis; in this study, however, the possibility that TRF5 compensates for the absence of TRF4 has not been excluded (18).Trf4 and Trf5 are members of a distinct family of eukaryotic DNA polymerase (Pol) ␤-like nucleotidyltransferases (1), and a template-dependent DNA polymerase activity has been reported for Trf4 and named DNA polymerase (3, 25). More recently, the Trf4 and Trf5 proteins have been shown to interact with the C-terminal domain of Pol2, the catalytic subunit of Polε, and stimulation of Polε DNA synthetic activity was observed in the presence of Trf4 (7). In keeping with these observations, the Trf4/Trf5 proteins are located in the nucleus (12, 23).The Trf4/Trf5-related proteins from other euk...

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“…In addition to its catalytic activity on DNA, the enzyme has been shown to have other activities functioning as a ribonuclease and a kinase (5-7); its kinase activity has been shown to phosphorylate RNA splicing factors (5). Topo I may also play a role in chromatid condensation (8). In lower eukaryotic organisms, topo I seems to be dispensable, in part because of the fact that other topoisomerases can subserve its role in its absence.…”

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confidence: 99%

A Novel Nuclear Localization Signal in Human DNA Topoisomerase I

Mo¹,

Wang²,

Beck³

2000

Journal of Biological Chemistry

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DNA topoisomerase (topo) I is a nuclear enzyme that plays an important role in DNA metabolism. Based on conserved nuclear targeting sequences, four classic nuclear localization signals (NLSs) have been proposed at the N terminus of human topo I, but studies with yeast have suggested that only one of them (amino acids (aa) 150 -156) is sufficient to direct the enzyme to the nucleus. In this study, we expressed human topo I fused to enhanced green fluorescent protein (EGFP) in mammalian cells and demonstrated that whereas aa 150 -156 are sufficient for nuclear localization, the nucleolar localization requires aa 157-199. More importantly, we identified a novel NLS within aa 117-146. In contrast to the classic NLSs that are rich in basic amino acids, the novel NLS identified in this study is rich in acidic amino acids. Furthermore, this novel NLS alone is sufficient to direct not only EGFP into the nucleus but also topo I; and the EGFP⅐topo I fusion driven by the novel NLS is as active in vivo as the wild-type topo I in response to the topo I inhibitor topotecan. Together, our results suggest that human topo I carries two independent NLSs that have opposite amino acid compositions.

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Mitotic chromosome condensation in the rDNA requires TRF4 and DNA topoisomerase I in Saccharomyces cerevisiae.

Cited by 112 publications

References 49 publications

Chromosome Condensation Factor Brn1p Is Required for Chromatid Separation in Mitosis

Chromosome Condensation Factor Brn1p Is Required for Chromatid Separation in Mitosis

Trf4 and Trf5 Proteins of Saccharomyces cerevisiae Exhibit Poly(A) RNA Polymerase Activity but No DNA Polymerase Activity

A Novel Nuclear Localization Signal in Human DNA Topoisomerase I

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