Ctf7p/Eco1p exhibits acetyltransferase activity–but does it matter?

Brands, Alex; Skibbens, Robert V.

doi:10.1016/j.cub.2004.12.052

Cited by 36 publications

(36 citation statements)

References 16 publications

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“…Since interaction was also detected with RFC and with the DNA damage checkpoint Rad24-RFC complex, it is likely that this interaction with Ctf7 is mediated through the small subunits of RFC common to all these complexes. Ctf7 is a lysine acetylase, although the importance of the acetylation of Ctf7 for establishing sister chromatid cohesion has been called into question (3,20). Therefore, it remains unclear how the demonstrated genetic link between Ctf7 and PCNA can be put into a mechanistic framework to further clarify the role of Ctf18-RFC in the establishment of chromatid cohesion through loading/unloading of PCNA.…”

Section: Discussionmentioning

confidence: 99%

Replication Protein A-Directed Unloading of PCNA by the Ctf18 Cohesion Establishment Complex

Bylund

Burgers

2005

Molecular and Cellular Biology

124

145

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The replication clamp PCNA is loaded around DNA by replication factor C (RFC) and functions in DNA replication and repair. Regulated unloading of PCNA during the progression and termination of DNA replication may require additional factors. Here we show that a Saccharomyces cerevisiae complex required for the establishment of sister chromatid cohesion functions as an efficient unloader of PCNA. Unloading requires ATP hydrolysis. This seven-subunit Ctf18-RFC complex consists of the four small subunits of RFC, together with Ctf18, Dcc1, and Ctf8. Ctf18-RFC was also a weak loader of PCNA onto naked template-primer DNA. However, when the single-stranded DNA template was coated by the yeast single-stranded DNA binding protein replication protein A (RPA) but not by a mutant form of RPA or a heterologous single-stranded DNA binding protein, both binding of Ctf18-RFC to substrate DNA and loading of PCNA were strongly inhibited, and unloading predominated. Neither yeast RFC itself nor two other related clamp loaders, containing either Rad24 or Elg1, catalyzed significant unloading of PCNA. The Dcc1 and Ctf8 subunits of Ctf18-RFC, while required for establishing sister chromatid cohesion in vivo, did not function specifically in PCNA unloading in vitro, thereby separating the functionality of the Ctf18-RFC complex into two distinct paths.The process of sister chromatid cohesion ensures that replicated chromosomes are distributed equally to progeny cells during cell division. Cohesion is mediated through a large ring-like structure, cohesin, which is deposited on the chromosomes in the late G 1 phase of the cell cycle. Sister chromatid cohesion is established during S phase, presumably by the actual passage of the replication fork. Several models exist by which cohesin is proposed to interact with the duplicated chromosomes in order to mediate cohesion. These models are based either on the idea that one cohesin ring encircles both sister chromosomes or on the idea that cohesion is mediated by the interlocking of two cohesin rings, with each ring more peripherally associated with a daughter chromosome (reviewed in references 33, 34, and 48). If the first type of model is correct, the mere passage of the replication fork through a cohesin ring would invariably ensure that the two sister chromatids stay attached until mitosis. However, the disadvantage of this elegant solution to the chromosome sorting problem is that it may be problematic for the replication fork to pass through the estimated 30-to 40-nm hole of the cohesin ring. Recent studies have shown that cohesin is specifically redistributed along the chromosome to transcription termination sites in a transcription-dependent manner, suggesting that the actual transcription machinery may push the cohesin rings ahead of the transcription bubble (26). If this is caused by steric problems because of the size of the transcription apparatus, similar steric problems may also occur with passage of the replication fork. Failure to establish sister chromatid cohesion would resul...

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Section: Discussionmentioning

confidence: 99%

Replication Protein A-Directed Unloading of PCNA by the Ctf18 Cohesion Establishment Complex

Bylund

Burgers

2005

Molecular and Cellular Biology

124

145

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“…Strains used in this study are listed in Table 1. Sectoring analyses to identify plasmid-dependent functions were based on previous genetic analyses and performed as previously described with minor modification (Koshland et al 1985;Krantz and Holm 1990;Brands and Skibbens 2005).…”

Section: Methodsmentioning

confidence: 99%

Sister Chromatid Cohesion Role for CDC28-CDK in Saccharomyces cerevisiae

Brands

Skibbens

2008

Genetics

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High-fidelity chromosome segregation requires that the sister chromatids produced during S phase also become paired during S phase. Ctf7p (Eco1p) is required to establish sister chromatid pairing specifically during DNA replication. However, Ctf7p also becomes active during G 2 /M in response to DNA damage. Ctf7p is a phosphoprotein and an in vitro target of Cdc28p cyclin-dependent kinase (CDK), suggesting one possible mechanism for regulating the essential function of Ctf7p. Here, we report a novel synthetic lethal interaction between ctf7 and cdc28. However, neither elevated CDC28 levels nor CDC28 Cak1p-bypass alleles rescue ctf7 cell phenotypes. Moreover, cells expressing Ctf7p mutated at all full-and partial-consensus CDKphosphorylation sites exhibit robust cell growth. These and other results reveal that Ctf7p regulation is more complicated than previously envisioned and suggest that CDK acts in sister chromatid cohesion parallel to Ctf7p reactions.

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“…The involvement of protein acetylation in the establishment of cohesion has also been suggested by a genetic study in Drosophila: An Eco1/Ctf7-like protein known as Deco and a protein belonging to a different class of acetyl-transferases named San are both required to prevent precocious sister chromatid separation (Williams et al 2003). Nonetheless, a mutation in the key catalytic residue of Eco1/Ctf7 does not compromise high-fidelity chromosome transmission in yeast (Brands and Skibbens 2005), a result that casts doubt on the functional relevance of the acetyl-transferase activity in cohesion establishment. Eco1/Ctf7 interacts genetically with the sliding clamp PCNA as well as with the clamp loader replication factor C (RF-C) (Kenna and Skibbens 2003), further suggesting its role in linking cohesion to DNA replication.…”

Section: Building the Linkage Between Sister Chromatidsmentioning

confidence: 96%

Dynamic molecular linkers of the genome: the first decade of SMC proteins

Losada¹,

Hirano²

2005

Genes Dev.

331

311

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Structural maintenance of chromosomes (SMC) proteins are chromosomal ATPases, highly conserved from bacteria to humans, that play fundamental roles in many aspects of higher-order chromosome organization and dynamics. In eukaryotes, SMC1 and SMC3 act as the core of the cohesin complexes that mediate sister chromatid cohesion, whereas SMC2 and SMC4 function as the core of the condensin complexes that are essential for chromosome assembly and segregation. Another complex containing SMC5 and SMC6 is implicated in DNA repair and checkpoint responses. The SMC complexes form unique ring-or V-shaped structures with long coiled-coil arms, and function as ATP-modulated, dynamic molecular linkers of the genome. Recent studies shed new light on the mechanistic action of these SMC machines and also expanded the repertoire of their diverse cellular functions. Dissecting this class of chromosomal ATPases is likely to be central to our understanding of the structural basis of genome organization, stability, and evolution.The chromosome is at the heart of all genetic processes. Its precise duplication and segregation are arguably the most important goal of the mitotic cell cycle, and programmed expression of its content, either genetic or epigenetic, is central to the development of an organism. While the astonishing advancement of genome biology in recent years has provided an advanced starting point for virtually all areas in biology, it does not solve an old problem in chromosome biology: How is the genomic DNA folded, organized, and segregated in the tiny space of a cell? The discovery of structural maintenance of chromosomes (SMC) proteins, almost a decade ago, provided a decisive clue to solve this longstanding question, and led to the identification of cohesin and condensins, two representative classes of SMC-containing complexes in eukaryotes. The proposed actions of cohesin and condensins offer a plausible, if not complete, explanation for the sudden appearance of thread-like "substances" (the chromosomes) and their longitudinal splitting during mitosis, first described by Walther Flemming (1882). Remarkably, SMC proteins are conserved among the three phyla of life, indicating that the basic strategy of chromosome organization may be evolutionarily conserved from bacteria to humans. An emerging theme is that SMC proteins are dynamic molecular linkers of the genome that actively fold, tether, and manipulate DNA strands. Their diverse functions range far beyond chromosome segregation, and involve nearly all aspects of chromosome behavior including chromosome-wide or long-range gene regulation and DNA repair. In this review article, we summarize our current understanding of SMC proteins with a major focus on studies published during the past three years. We start by describing the architecture and mechanistic actions of SMC protein complexes, and then discuss how the concerted actions of cohesin and condensin support the faithful segregation of chromosomes during mitosis and meiosis. Finally, emerging studies of a third S...

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Ctf7p/Eco1p exhibits acetyltransferase activity–but does it matter?

Cited by 36 publications

References 16 publications

Replication Protein A-Directed Unloading of PCNA by the Ctf18 Cohesion Establishment Complex

Replication Protein A-Directed Unloading of PCNA by the Ctf18 Cohesion Establishment Complex

Sister Chromatid Cohesion Role for CDC28-CDK in Saccharomyces cerevisiae

Dynamic molecular linkers of the genome: the first decade of SMC proteins

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