Translocation and Stability of Replicative DNA Helicases upon Encountering DNA-Protein Cross-links

Nakano, Toshiaki; Miyamoto-Matsubara, Mayumi; Shoulkamy, Mahmoud I.; Salem, Amir M.H.; Pack, Seung Pil; Ishimi, Yukio; Ide, Hiroshi

doi:10.1074/jbc.m112.419358

Cited by 62 publications

(61 citation statements)

References 61 publications

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“…DPCs, if left unrepaired, inhibit transcription as well as DNA unwinding during replication and may therefore result in genome instability or even cell death (Barker et al, 2005;Fu et al, 2011;Kohn et al, 2000;Nakano et al, 2013). Studies in yeast indicated that homologous recombination (HR) and nucleotide excision repair (NER) contribute to resistance toward FA exposure (de Graaf et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

A DNA-Dependent Protease Involved in DNA-Protein Crosslink Repair

Stingele

Schwarz

Bloemeke

et al. 2014

Cell

235

391

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Toxic DNA-protein crosslinks (DPCs) arise by ionizing irradiation and UV light, are particularly caused by endogenously produced reactive compounds such as formaldehyde, and also occur during compromised topoisomerase action. Although nucleotide excision repair and homologous recombination contribute to cell survival upon DPCs, hardly anything is known about mechanisms that target the protein component of DPCs directly. Here, we identify the metalloprotease Wss1 as being crucial for cell survival upon exposure to formaldehyde and topoisomerase 1-dependent DNA damage. Yeast mutants lacking Wss1 accumulate DPCs and exhibit gross chromosomal rearrangements. Notably, in vitro assays indicate that substrates such as topoisomerase 1 are processed by the metalloprotease directly and in a DNA-dependent manner. Thus, our data suggest that Wss1 contributes to survival of DPC-harboring cells by acting on DPCs proteolytically. We propose that DPC proteolysis enables repair of these unique lesions via downstream canonical DNA repair pathways.

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Section: Introductionmentioning

confidence: 99%

A DNA-Dependent Protease Involved in DNA-Protein Crosslink Repair

Stingele

Schwarz

Bloemeke

et al. 2014

Cell

235

391

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“…azadC is incorporated into DNA and covalently traps the reaction intermediate of DNA cytosine methyltransferase, giving rise to DNA-protein cross-links (DPCs) [31]. DPCs block DNA replication and transcription [32,33] and hence constitute the major lethal lesions upon treatment with azadC. cisPt is a bifunctional DNA-damaging The treated cells were further incubated in fresh medium for 6 days, and colonies were scored to calculate the surviving fraction.…”

Section: Discussionmentioning

confidence: 99%

Depletion of RUVBL2 in Human Cells Confers Moderate Sensitivity to Anticancer Agents

Matsubara¹

2014

J Cancer Sci Ther

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IntroductionRuvB-like 1 (RUVBL1, also known as RVB1, TIP49A and Pontin) and RuvB-like 2 (RUVBL2, also known as RVB2, TIP49B and Reptin) belong to the family of ATPases associated with various cell activities (AAA+ ATPase), and are part of large protein complexes that are involved in chromatin remodeling, transcription regulation, DNA damage responses and repair, and the biogenesis of small nucleolar ribonucleoproteins [1,2]. RUVBL1 and RUVBL2 (RUVBLs) share about 45% identity and 60% similarity in the amino acid sequence and are homologous to the prokaryotic RuvB helicase [3,4]. Remarkably, RUVBL1 depletion leads to down regulation of RUVBL2, and vice versa [5]. RUVBLs also interact with oncogenes such as c-Myc and β-catenin and are implicated in cancer [4,6]. Since RUVBLs participate in many aspects of cellular functions, links between these functions are currently being studied extensively.In human cells, RUVBLs serve as the essential components of the TIP60 histone acetyltransferase complex. TIP60 is recruited to DNA damage sites [7,8] and plays multiple roles in DNA damage responses [9]. After treatment with various DNA-damaging agents, RUVBL1 is required for the dephosphorylation of phosphorylated histone H2AX, a marker of DNA double-strand breaks (DSBs), through the histone acetyltransferase activity of TIP60 [8]. Likewise, depletion of RUVBL2 increases the persistence of phosphorylated histone H2AX upon treatment with X-rays [10]. Apart from the pathway involving the TIP60 complex, RUVBLs regulate the abundance and activity of phosphatidylinositol 3-kinases such as ataxia telangiectasia mutated (ATM), ATM-and Rad3-related (ATR) kinase, and DNA-dependent protein kinase (DNA-PK) that sense and activate the DNA damage signal [11]. RUVBLs are also components of the INO80 chromatin remodeling complex that is recruited to the DSB site. A recent study has shown that the mammalian INO80 complex mediates DSB repair through its role in DNA end resection [12]. The ATP-dependent helicase activity of RUVBLs demonstrated in vitro may be involved in the processing of resected DNA ends [13,14]. Depletion of RUVBLs in human cells impairs the recruitment of the RAD51 recombinase to the DSB site following DNA end resection [15]. Consistent with the finding, it has been shown that the functional inactivation or depletion of TIP60 that contains RUVBLs in mouse and human cells impairs the recruitment of RAD51 to the DSB site [16].The aforementioned studies have afforded mechanistic insights into the function of human RUVBLs in DNA damage responses and repair. However, few studies have investigated the role of RUVBLs in

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“…Indeed, DPCs form strong blocks for transcription by RNA polymerases when located on the transcribed strand 22 . Furthermore, DPCs (and DPC-mimicking biotin-streptavidin adducts) have been shown to inhibit the unwinding of the DNA duplex during replication in vitro 23,24 and, consequently, to interfere with replicationfork progression in vivo 25 . Interestingly, the effect of DPCs on the replicative helicase depends on whether they are located on the leading or the lagging strand 23,24 (FIG.…”

Section: Toxicity and Effects Of Dpcsmentioning

confidence: 99%

“…Hence, results obtained from studying specific DPCs might not always be generally extendable to others. Indeed, small DPCs (up to approximately 10 kDa) do not seem to inhibit replicative helicases 23 , and even the way and orientation in which a protein is crosslinked to DNA seems to be a crucial parameter for helicase stalling 23 . At any rate, DPCs interfere with DNA replication at various levels, and it is thus not surprising that DPC-inducing agents, such as formaldehyde, cause genomic instability, which manifests in micronuclei relieves torsional stress within DNA molecules by nicking one of the DNA strands.…”

Section: Toxicity and Effects Of Dpcsmentioning

confidence: 99%

DNA–protein crosslink repair

Stingele

Jentsch

2015

Nat Rev Mol Cell Biol

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DNA-protein crosslinks (DPCs) are highly toxic DNA adducts, but whether dedicated DPC-repair mechanisms exist was until recently unknown. This has changed with discoveries made in yeast and Xenopus laevis that revealed a protease-based DNA-repair pathway specific for DPCs. Importantly, mutations in the gene encoding the putative human homologue of a yeast DPC protease cause a human premature ageing and cancer predisposition syndrome. Thus, DPC repair is a previously overlooked genome-maintenance mechanism that may be essential for tumour suppression.

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Translocation and Stability of Replicative DNA Helicases upon Encountering DNA-Protein Cross-links

Cited by 62 publications

References 61 publications

A DNA-Dependent Protease Involved in DNA-Protein Crosslink Repair

A DNA-Dependent Protease Involved in DNA-Protein Crosslink Repair

Depletion of RUVBL2 in Human Cells Confers Moderate Sensitivity to Anticancer Agents

DNA–protein crosslink repair

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