Sap1p Binds to Ter1 at the Ribosomal DNA of Schizosaccharomyces pombe and Causes Polar Replication Fork Arrest

Krings, Gregor; Bastia, Deepak

doi:10.1074/jbc.m508996200

Cited by 53 publications

(75 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SAS1 is known to interact with the Sap1 protein, another trans-acting factor that is also thought to be required for mating-type switching (Arcangioli et al 1994a). Interestingly, recent studies have shown that Sap1 also binds the Ter1/RFB1 sequence, which has strong homology to SAS1 and is required for fork pausing at the rDNA loci (Krings and Bastia 2005;Mejia-Ramirez et al 2005). The mechanisms by which the FPC and Sap1 contribute to programmed fork pausing are largely unknown, however.…”

mentioning

confidence: 99%

Sap1 Promotes the Association of the Replication Fork Protection Complex With Chromatin and Is Involved in the Replication Checkpoint in Schizosaccharomyces pombe

Noguchi

2007

Genetics

View full text Add to dashboard Cite

Sap1 is involved in replication fork pausing at rDNA repeats and functions during mating-type switching in Schizosaccharomyces pombe. These two roles are dependent on the ability of Sap1 to bind specific DNA sequences at the rDNA and mating-type loci, respectively. In S. pombe, Swi1 and Swi3 form the replication fork protection complex (FPC) and play important roles in the activation of the replication checkpoint and the stabilization of stalled replication forks. Here we describe the roles of Sap1 in the replication checkpoint. We show that Sap1 is involved in the activation of the replication checkpoint kinase Cds1 and that sap1 mutant cells accumulate spontaneous DNA damage during the S-and G2-phases, which is indicative of fork damage. We also show that sap1 mutants have a defect in the resumption of DNA replication after fork arrest. Sap1 is localized at the replication origin ori2004 and this localization is required for the association of the FPC with chromatin. We propose that Sap1 is required to recruit the FPC to chromatin, thereby contributing to the activation of the replication checkpoint and the stabilization of replication forks.

show abstract

mentioning

confidence: 99%

Sap1 Promotes the Association of the Replication Fork Protection Complex With Chromatin and Is Involved in the Replication Checkpoint in Schizosaccharomyces pombe

Noguchi

2007

Genetics

View full text Add to dashboard Cite

show abstract

“…In contrast, RFB1 is similar to the budding yeast RFB. RFB1 is bound by the switchactivating protein Sap1 to generate a polar replication fork arrest (Krings and Bastia, 2005;Mejia-Ramirez et al, 2005). DNA helicases of the RecQ family play a central role in maintaining genome stability (Enomoto, 2001;Opresko et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rad22^Rad52-dependent Repair of Ribosomal DNA Repeats Cleaved by Slx1-Slx4 Endonuclease

Coulon

Noguchi

et al. 2006

MBoC

View full text Add to dashboard Cite

Slx1 and Slx4 are subunits of a structure-specific DNA endonuclease that is found in Saccharomyces cerevisiae, Schizosaccharomyces pombe, and other eukaryotic species. It is thought to initiate recombination events or process recombination structures that occur during the replication of the tandem repeats of the ribosomal DNA (rDNA) locus. Here, we present evidence that fission yeast Slx1-Slx4 initiates homologous recombination events in the rDNA repeats that are processed by a mechanism that requires Rad22 (Rad52 homologue) but not Rhp51 (Rad51 homologue). Slx1 is required to generate ϳ50% of the spontaneous Rad22 DNA repair foci that occur in cycling cells. Most of these foci colocalize with the nucleolus, which contains the rDNA repeats. The increased fork pausing at the replication fork barriers in the rDNA repeats in a strain that lacks Rqh1 DNA helicase is further increased by expression of a dominant negative form of Slx1. These data suggest that Slx1-Slx4 cleaves paused replication forks in the rDNA, leading to Rad22-dependent homologous recombination that is used to maintain rDNA copy number. INTRODUCTIONWhile replicating the genome, DNA polymerases will sometimes stall when they encounter DNA lesions, protein complexes bound to DNA, or nucleotide starvation. Stalled forks pose serious threats to genomic integrity because they are prone to collapse or rearrangement (McGlynn and Lloyd, 2002). In contrast, there are many examples of natural replication pause and termination sites in a variety of organisms (Rothstein et al., 2000). These sites are often called replication fork barriers (RFBs). It is somewhat paradoxical that in some cases these "programmed" RFBs are thought to play important roles in maintaining genome integrity.The best-characterized RFBs occur in the ribosomal DNA genes (rDNA), which are present in long tandem repeats at one or a few chromosomal loci in most eukaryotic species, including yeasts and humans (Brewer and Fangman, 1988;Linskens and Huberman, 1988;Little et al., 1993;Gerber et al., 1997;Sanchez et al., 1998). The budding yeast Saccharomyces cerevisiae carries ϳ150 copies of the rDNA genes. The RFB is located in the nontranscribed sequence (NTS) between the 3Ј end of the 35S rRNA gene and the autonomously replicating sequence (ARS). The RFB inhibits replication fork progression in the direction opposite to rDNA transcription. This mechanism helps to prevent collisions between replication forks and the transcription machinery (Takeuchi et al., 2003). The protein fork blocking 1 (Fob1) binds DNA in the RFB region and is essential for RFB activity (Kobayashi and Horiuchi, 1996).The size of the rDNA array in S. cerevisiae is not static. For example, it will contract upon inactivation of RNA polymerase I and expands after RNA polymerase I activity is restored (Kobayashi et al., 1998). Fob1 is required for the mechanisms that control the copy number of rDNA repeats (Kobayashi et al., 2001;Johzuka and Horiuchi, 2002). The current model for the regulation of the rDNA copy number involv...

show abstract

“…Sap1 has been suggested to play an important role in replication fork pausing at rDNA and retrotransposon LTRs (18,20,21). We show that Sap1 also facilitates replication progression, as indicated by 2D gel, Mcm6 localization, and BrdU incorporation analyses.…”

Section: Discussionmentioning

confidence: 73%

“…Sap1 is an abundant nuclear protein that binds specific DNA elements distributed across the genome (17,18). Multiple functions for Sap1 have been proposed, including a role in replication fork blocking (19)(20)(21), replication checkpoint activation (22), and genome organization (17). To gain further insight, we examined Sap1 subcellular localization.…”

Section: Resultsmentioning

confidence: 99%

Shelterin components mediate genome reorganization in response to replication stress

Mizuguchi

Taneja

Matsuda

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The dynamic nature of genome organization impacts critical nuclear functions including the regulation of gene expression, replication, and DNA damage repair. Despite significant progress, the mechanisms responsible for reorganization of the genome in response to cellular stress, such as aberrant DNA replication, are poorly understood. Here, we show that fission yeast cells carrying a mutation in the DNA-binding protein Sap1 show defects in DNA replication progression and genome stability and display extensive changes in genome organization. Chromosomal regions such as subtelomeres that show defects in replication progression associate with the nuclear envelope in sap1 mutant cells. Moreover, highresolution, genome-wide chromosome conformation capture (Hi-C) analysis revealed prominent contacts between telomeres and chromosomal arm regions containing replication origins proximal to binding sites for Taz1, a component of the Shelterin telomere protection complex. Strikingly, we find that Shelterin components are required for interactions between Taz1-associated chromosomal arm regions and telomeres. These analyses reveal an unexpected role for Shelterin components in genome reorganization in cells experiencing replication stress, with important implications for understanding the mechanisms governing replication and genome stability.T he 3D organization of the eukaryotic genome creates specialized microenvironments that play important roles in various nuclear processes (1). In addition to regulation of gene expression, proper execution of the DNA replication program and DNA damage repair also involve dynamic organization of the genome (2, 3). Indeed, computational analyses indicate spatial segregation of replication origins based on their timing of firing during S-phase (4), suggesting that besides local chromatin structure, the 3D organization of chromosomes is an important contributing factor in the spatiotemporal control of replication (5, 6). Despite important advances, understanding the connections between diverse chromosomal events and genome organization remains an important challenge.The complexities of genome organization have been studied in several model organisms, including the fission yeast Schizosaccharomyces pombe, for which the 3D organization has been explored at high resolution (7,8). This simple eukaryote contains the basic chromosomal elements of more complex systems, including partitioning of the genome into euchromatin and heterochromatin domains. The S. pombe genome conforms to a Rabl organization pattern in which centromere clusters and telomere clusters are anchored at opposing sides of the nuclear periphery (9, 10). In addition, two key elements shape genome architecture: cohesin-dependent locally crumpled 50-to 100-kb repeating elements called "globules" on chromosome arms and the constraints imposed by the compaction of the chromatin fiber by heterochromatin domains such as at pericentromeric regions (8). The relatively small size of the S. pombe genome combined with the conserved genome...

show abstract

Sap1p Binds to Ter1 at the Ribosomal DNA of Schizosaccharomyces pombe and Causes Polar Replication Fork Arrest

Cited by 53 publications

References 45 publications

Sap1 Promotes the Association of the Replication Fork Protection Complex With Chromatin and Is Involved in the Replication Checkpoint in Schizosaccharomyces pombe

Sap1 Promotes the Association of the Replication Fork Protection Complex With Chromatin and Is Involved in the Replication Checkpoint in Schizosaccharomyces pombe

Rad22^Rad52-dependent Repair of Ribosomal DNA Repeats Cleaved by Slx1-Slx4 Endonuclease

Shelterin components mediate genome reorganization in response to replication stress

Contact Info

Product

Resources

About

Sap1p Binds to Ter1 at the Ribosomal DNA of Schizosaccharomyces pombe and Causes Polar Replication Fork Arrest

Cited by 53 publications

References 45 publications

Sap1 Promotes the Association of the Replication Fork Protection Complex With Chromatin and Is Involved in the Replication Checkpoint in Schizosaccharomyces pombe

Sap1 Promotes the Association of the Replication Fork Protection Complex With Chromatin and Is Involved in the Replication Checkpoint in Schizosaccharomyces pombe

Rad22Rad52-dependent Repair of Ribosomal DNA Repeats Cleaved by Slx1-Slx4 Endonuclease

Shelterin components mediate genome reorganization in response to replication stress

Contact Info

Product

Resources

About

Rad22^Rad52-dependent Repair of Ribosomal DNA Repeats Cleaved by Slx1-Slx4 Endonuclease