Regulation of Rtt107 Recruitment to Stalled DNA Replication Forks by the Cullin Rtt101 and the Rtt109 Acetyltransferase

Roberts, Tania Michelle; Zaidi, Iram Waris; Vaisica, Jessica A.; Peter, Matthias; Brown, Grant W.

doi:10.1091/mbc.e07-09-0961

Cited by 55 publications

(88 citation statements)

References 64 publications

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“…Deletion of RTT101 leads to several known phenotypes in budding yeast, including an increase in transposition of Ty1 elements (Scholes et al 2001) and delayed anaphase progression (Michel et al 2003). Recently, Rtt101p was shown to be required for progression of replication through damaged DNA and through natural replication-impeding loci (Luke et al 2006;Roberts et al 2008). It is possible that the partial BIR defect observed in our experiments results from problems associated with passage of BIR through areas on the donor chromosome that impede replication.…”

Section: Leumentioning

confidence: 74%

Defective Break-Induced Replication Leads to Half-Crossovers inSaccharomyces cerevisiae

et al. 2008

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Break-induced replication (BIR) is an important process of DNA metabolism that has been implicated in the restart of collapsed replication forks, as well as in various chromosomal instabilities, including loss of heterozygosity, translocations, and alternative telomere lengthening. Therefore, knowledge of how BIR is carried out and regulated is important for better understanding the maintenance of genomic stability in eukaryotes. Here we present a new yeast experimental system that enables the genetic control of BIR to be investigated. Analysis of mutations selected on the basis of their sensitivity to various DNA-damaging agents demonstrated that deletion of POL32, which encodes a third, nonessential subunit of polymerase d, significantly reduced the efficiency of BIR, although some POL32-independent BIR was still observed. Importantly, the BIR defect in pol32D cells was associated with the formation of half-crossovers. We propose that these half-crossovers resulted from aberrant processing of BIR intermediates. Furthermore, we suggest that the half-crossovers observed in our system are analogous to nonreciprocal translocations (NRTs) described in mammalian tumor cells and, thus, our system could represent an opportunity to further study the NRT mechanism in yeast.

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Section: Leumentioning

confidence: 74%

Defective Break-Induced Replication Leads to Half-Crossovers inSaccharomyces cerevisiae

et al. 2008

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“…The SLX4 gene interacts with genes involved in error-free DNA damage bypass and Slx4 is required for resistance to DNA alkylation during S-phase (Flott et al, 2007). This is thought to involve the interaction between Slx4 and the multi-BRCT domain protein Rtt107 (Flott et al, 2007;Roberts et al, 2006;Roberts et al, 2008). Rtt107 itself associates with Rtt101 CUL4 that is part of a ubiquitin (Ub) E3 ligase proposed to control protein turnover at stalled replication forks and promote replication through natural pause sites and DNA damage (Luke et al, 2006;Zaidi et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Human SLX4 Is a Holliday Junction Resolvase Subunit that Binds Multiple DNA Repair/Recombination Endonucleases

Fekairi¹,

Scaglione²,

Chahwan³

et al. 2009

Journal of End-to-End-testing

115

204

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SummaryStructure-specific endonucleases resolve DNA secondary structures generated during DNA repair and recombination. The yeast 5′-flap endonuclease Slx1-Slx4 has received particular attention with the finding that Slx4 has Slx1-independent key functions in genome maintenance. Although Slx1 is a highly conserved protein in eukaryotes, no orthologs of Slx4 were reported other than in fungi. Here we report the identification of Slx4 orthologs in metazoa, including fly MUS312, essential for meiotic recombination, and human BTBD12, an ATM/ATR checkpoint kinase substrate. Human SLX1-SLX4 displays robust Holliday junction resolvase activity in addition to 5′-flap endonuclease activity. Depletion of SLX1 and SLX4 results in 53BP1 foci accumulation and H2AX phosphorylation as well as cellular hypersensitivity to MMS. Furthermore, we show that SLX4 binds the XPF and MUS81 subunits of the XPF-ERCC1 and MUS81-EME1 endonucleases and is required for DNA interstrand crosslink repair. We propose that SLX4 acts as a docking platform for multiple structure-specific endonucleases.

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“…We found that similarly to ASF1, RTT109 is required in the absence of RRM3 ( Figure S2). Because RTT109 also acetylates other H3 and H4 lysines (Fillingham et al 2008;Abshiru et al 2013) and has functions independent of its H3K56 HAT activity (Roberts et al 2008), we crossed a strain expressing H3K56R from a centromeric plasmid as the sole source of histone H3 to an rrm3D strain and analyzed the spores after sporulation of the diploid. Results obtained from the dissection of 160 tetrads are presented in Table 1.…”

Section: H3k56 Acetylation Is Necessary For Viability Of Rrm3d Cellsmentioning

confidence: 99%

“…In the absence of RRM3, chromosome breaks occur at discrete fork pause sites at specific genomic locations (Ivessa et al 2003). A number of studies indicate that the DNA breaks generated in rrm3D cells affect cell viability in the absence of the so-called "H3K56 acetylation pathway" that comprises ASF1, RTT109, RTT101, MMS1, and MMS22 (Tong et al 2004;Luke et al 2006;Pan et al 2006;Collins et al 2007;Duro et al 2008;Roberts et al 2008;Zaidi et al 2008;Costanzo et al 2010;Koh et al 2010;Mimura et al 2010).In S. cerevisiae, H3K56 localizes at the DNA entry and exit points of a nucleosome (Masumoto et al 2005;Ozdemir et al 2005;Xu et al 2005). H3K56 is transiently acetylated during the S phase of the cell cycle and after DNA damage and is rapidly de-acetylated by the action of the sirtuins Hst3 and Hst4, when cells enter the transition between G2 and M phases and after DNA repair (Masumoto et al 2005;Xu et al 2005).…”

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confidence: 99%

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confidence: 99%

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Replisome Function During Replicative Stress Is Modulated by Histone H3 Lysine 56 Acetylation Through Ctf4

et al. 2015

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Histone H3 lysine 56 acetylation in Saccharomyces cerevisiae is required for the maintenance of genome stability under normal conditions and upon DNA replication stress. Here we show that in the absence of H3 lysine 56 acetylation replisome components become deleterious when replication forks collapse at natural replication block sites. This lethality is not a direct consequence of chromatin assembly defects during replication fork progression. Rather, our genetic analyses suggest that in the presence of replicative stress H3 lysine 56 acetylation uncouples the Cdc45-Mcm2-7-GINS DNA helicase complex and DNA polymerases through the replisome component Ctf4. In addition, we discovered that the N-terminal domain of Ctf4, necessary for the interaction of Ctf4 with Mms22, an adaptor protein of the Rtt101-Mms1 E3 ubiquitin ligase, is required for the function of the H3 lysine 56 acetylation pathway, suggesting that replicative stress promotes the interaction between Ctf4 and Mms22. Taken together, our results indicate that Ctf4 is an essential member of the H3 lysine 56 acetylation pathway and provide novel mechanistic insights into understanding the role of H3 lysine 56 acetylation in maintaining genome stability upon replication stress. KEYWORDS Ctf4; H3K56 acetylation; Mms22; replicative stress; replisome T HE eukaryotic replisome consists of polymerases and an essential DNA helicase that are linked by a number of factors assembled during the initiation of chromosome replication. Progression of the replication fork depends on the activity of the replisome progression complex (RPC). This complex is uniquely present during S phase (Gambus et al. 2006) and remains associated with the replication fork until completion of DNA replication. In Saccharomyces cerevisiae, the RPC is made up of Mcm10, Mrc1, Tof1, Csm3, Ctf4, Top1, FACT (Spt16 and Pob3), and the CMG complex comprising Cdc45, , and the go ichi ni san (GINS) complex. The CMG constitutes the core replicative helicase responsible for the movement and activities of the replication fork (Pacek et al. 2006;Bochman and Schwacha 2009).The link between helicase and polymerases is a crucial determinant for the regulation of the replisome. The leadingstrand DNA polymerase-ɛ was recently shown to be integrated into the replisome via an interaction with the GINS complex (Sengupta et al. 2013). Furthermore, the DNA polymerasea-primase complex, which initiates DNA synthesis at replication origins and continues to prime Okazaki fragments at the fork, remains associated with the RPC via the Ctf4 trimer, which simultaneously interacts with the GINS complex (Gambus et al. 2009;Tanaka et al. 2009;Gosnell and Christensen 2011;Simon et al. 2014).Cells have evolved different mechanisms to maintain genome integrity under the conditions threatening replication progression (Jossen and Bermejo 2013;Leman and Noguchi 2013). The S-phase checkpoint mediated by MRC1 was initially characterized as a pathway activated by fork stalling and able to both stabilize the replisome and dela...

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Regulation of Rtt107 Recruitment to Stalled DNA Replication Forks by the Cullin Rtt101 and the Rtt109 Acetyltransferase

Cited by 55 publications

References 64 publications

Defective Break-Induced Replication Leads to Half-Crossovers inSaccharomyces cerevisiae

Defective Break-Induced Replication Leads to Half-Crossovers inSaccharomyces cerevisiae

Human SLX4 Is a Holliday Junction Resolvase Subunit that Binds Multiple DNA Repair/Recombination Endonucleases

Replisome Function During Replicative Stress Is Modulated by Histone H3 Lysine 56 Acetylation Through Ctf4

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