Relationships between chromatin remodeling and DNA damage repair induced by 8-methoxypsoralen and UVA in yeast Saccharomyces cerevisiae

Cruz, Lavínia Almeida; Guecheva, Temenouga Nikolova; Bonato, Diego; Henriques, João Antônio Pêgas

doi:10.1590/s1415-47572012000600021

Cited by 8 publications

(10 citation statements)

References 51 publications

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“…To examine whether FANCA interacts with MUS81-EME1 in vivo , we created site-specific ICL damages in living human cells. It has been reported that cells treated with 8-MOP form ICL damages after light activation ( 50 , 51 ). To determine the dynamics of FANCA responding to ICL damage, we expressed Green fluorescent protein (GFP)-FANCA in U2OS cells and visualized them through confocal microscopy.…”

Section: Resultsmentioning

confidence: 99%

Damage-dependent regulation of MUS81-EME1 by Fanconi anemia complementation group A protein

Benitez¹,

Yuan²,

Nakajima³

et al. 2013

Nucleic Acids Research

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MUS81-EME1 is a DNA endonuclease involved in replication-coupled repair of DNA interstrand cross-links (ICLs). A prevalent hypothetical role of MUS81-EME1 in ICL repair is to unhook the damage by incising the leading strand at the 3′ side of an ICL lesion. In this study, we report that purified MUS81-EME1 incises DNA at the 5′ side of a psoralen ICL residing in fork structures. Intriguingly, ICL repair protein, Fanconi anemia complementation group A protein (FANCA), greatly enhances MUS81-EME1-mediated ICL incision. On the contrary, FANCA exhibits a two-phase incision regulation when DNA is undamaged or the damage affects only one DNA strand. Studies using truncated FANCA proteins indicate that both the N- and C-moieties of the protein are required for the incision regulation. Using laser-induced psoralen ICL formation in cells, we find that FANCA interacts with and recruits MUS81 to ICL lesions. This report clarifies the incision specificity of MUS81-EME1 on ICL damage and establishes that FANCA regulates the incision activity of MUS81-EME1 in a damage-dependent manner.

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Section: Resultsmentioning

confidence: 99%

Damage-dependent regulation of MUS81-EME1 by Fanconi anemia complementation group A protein

Benitez¹,

Yuan²,

Nakajima³

et al. 2013

Nucleic Acids Research

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“…During DSB repair, the condensed chromatin structure prevents the access of repair factors to the broken DNA. Swi/Snf in yeast has been defined as an important chromatin remodeller and transcriptional regulator in DSB repair (Cruz et al, 2012). Recent studies using mammalian cells have shown that BRG1 (the ATPase subunit of SWI/SNF) can be recruited to DSBs by interacting with cH2AX-containing nucleosomes (Lee et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that SWI/SNF promotes the phosphorylation of H2AX Ser139 and is vital for the cell response to DSBs in human cells (Park et al, 2006;Ray et al, 2009;Lee et al, 2010). Yeast mutants lacking SWI/SNF activity are sensitive to DNA damaging agents that cause DSBs, and the synapsis between the invading MATa ssDNA and HMLa DNA is blocked in these mutants (Cruz et al, 2012;Chai et al, 2005). BRG1, the core ATPase subunit of the SWI/SNF complex, is recruited to DSB sites, where it directly interacts with cH2AX-containing nucleosomes.…”

Section: Introductionmentioning

confidence: 99%

BRG1 promotes DNA double-strand break repair by facilitating the replacement of RPA with RAD51

Wang

Chen

et al. 2014

Journal of Cell Science

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DNA double-strand breaks (DSBs) are a type of lethal DNA damage. The repair of DSBs requires tight coordination between the factors modulating chromatin structure and the DNA repair machinery. BRG1, the ATPase subunit of the chromatin remodelling complex Switch/Sucrose non-fermentable (SWI/SNF), is often linked to tumorigenesis and genome instability, and its role in DSB repair remains largely unclear. In the present study, we show that BRG1 is recruited to DSB sites and enhances DSB repair. Using DR-GFP and EJ5-GFP reporter systems, we demonstrate that BRG1 facilitates homologous recombination repair rather than nonhomologous end-joining (NHEJ) repair. Moreover, the BRG1-RAD52 complex mediates the replacement of RPA with RAD51 on single-stranded DNA (ssDNA) to initiate DNA strand invasion. Loss of BRG1 results in a failure of RAD51 loading onto ssDNA, abnormal homologous recombination repair and enhanced DSBinduced lethality. Our present study provides a mechanistic insight into how BRG1, which is known to be involved in chromatin remodelling, plays a substantial role in the homologous recombination repair pathway in mammalian cells.

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“…8-MOP passively enters the cells where it intercalates into the DNA within 2 minutes [9, 10]. Upon irradiation with UVA photons, 8-MOP induces DNA cross-linking, which interferes with the cell replication machinery [11–14]. ECP treatment inhibits cell proliferation and induces T-cell apoptosis and the release of immunomodulatory cytokines [6–8].…”

Section: Introductionmentioning

confidence: 99%

A standardized methodical approach to characterize the influence of key parameters on the in vitro efficacy of extracorporeal photopheresis

et al. 2019

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Extracorporeal photopheresis (ECP) is an autologous immunomodulatory cell therapy that consists of the ex vivo collection of mononuclear cells (MNCs), which are irradiated with UVA in the presence of the photosensitizing agent 8-methoxypsoralen (8-MOP) to induce cell apoptosis. This photoactivated cell preparation is then reinfused into the patient. While the clinical benefits of ECP are well-demonstrated, no study has yet characterized the influence of variations in the composition of the cell preparation on the efficacy of ECP in vitro . Here, we describe a standardized methodology for the in vitro assessment of ECP that uses the human lymphoma T-cell line and mimics the clinical procedure. By quantifying cell apoptosis, inhibition of cell proliferation, and 8-MOP consumption, we used this approach to characterize the specific influence of key variables on the cellular response to ECP. We found that (i) increases in hematocrit and plasma concentrations attenuated the cellular response to ECP; (ii) plasma concentration was the only variable tested that influenced 8-MOP consumption; and (iii) the loss of efficacy due to variations in the concentration of certain blood components could be counteracted by modulating the UVA dose. This methodology may enable evaluation of other leukapheresis preparation protocols and better determination of the optimal working parameters for ECP.

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Relationships between chromatin remodeling and DNA damage repair induced by 8-methoxypsoralen and UVA in yeast Saccharomyces cerevisiae

Cited by 8 publications

References 51 publications

Damage-dependent regulation of MUS81-EME1 by Fanconi anemia complementation group A protein

Damage-dependent regulation of MUS81-EME1 by Fanconi anemia complementation group A protein

BRG1 promotes DNA double-strand break repair by facilitating the replacement of RPA with RAD51

A standardized methodical approach to characterize the influence of key parameters on the in vitro efficacy of extracorporeal photopheresis

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