Modulation of Homology-Directed Repair in T98G Glioblastoma Cells Due to Interactions between Wildtype p53, Rad51 and HCMV IE1-72

Kulkarni, Amit; Fortunato, Elizabeth A.

doi:10.3390/v6030968

Cited by 6 publications

(3 citation statements)

References 63 publications

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“…It was previously demonstrated that SPOC1 modulates DNA repair kinetics and is recruited to DNA doublestrand breaks in an ATM-dependent manner (24). Since there is increasing evidence that the IE1 protein is able to modulate the DNA damage response during HCMV infection, we assumed that IE1 might be involved in the upregulation of SPOC1 (27)(28)(29)(30). In order to investigate this, we utilized IE1-inducible HFF cells (HFF-IE1 Tet-On) and analyzed SPOC1 expression levels in the presence or absence of IE1 (Fig.…”

Section: Resultsmentioning

confidence: 98%

Chromatin-Remodeling Factor SPOC1 Acts as a Cellular Restriction Factor against Human Cytomegalovirus by Repressing the Major Immediate Early Promoter

Reichel

Stilp

Scherer³

et al. 2018

J Virol

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23The cellular protein SPOC1 (survival time-associated PHD finger protein in ovarian cancer 24 1) acts as a regulator of chromatin structure and DNA damage response. It binds 25H3K4me2/3 containing chromatin and promotes DNA condensation by recruiting 26 corepressors such as KAP-1 and H3K9 methyltransferases. Previous studies identified 27 SPOC1 as a restriction factor against human adenovirus (HAdV) infection that is 28 antagonized by E1B-55K/E4orf6-dependent proteasomal degradation. Here, we 29 demonstrate that, in contrast to HAdV-infected cells, SPOC1 is transiently upregulated 30 during the early phase of HCMV replication. We show that expression of the immediate-31 early protein 1 (IE1) is sufficient and necessary to induce SPOC1. Additionally, we 32 discovered that during later stages of infection SPOC1 is downregulated in a GSK-3β-33 dependent manner. We provide evidence that SPOC1 overexpression severely were known to mediate intrinsic immunity against HCMV. In this study, we identify the 52 chromatin modulator SPOC1 as a novel restriction factor against HCMV. We show that 53 pre-existing high SPOC1 protein levels mediate a silencing of HCMV gene expression via 54 a specific association with an important viral cis-regulatory element, the major immediate-55 early promoter. Since SPOC1 expression varies between cell-types, this factor may play 56 an important role in the tissue-specific defense against HCMV. 57

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Section: Resultsmentioning

confidence: 98%

Chromatin-Remodeling Factor SPOC1 Acts as a Cellular Restriction Factor against Human Cytomegalovirus by Repressing the Major Immediate Early Promoter

Reichel

Stilp

Scherer³

et al. 2018

J Virol

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“…Further research found that the IE1 protein, in a novel way, can activate flap endonuclease 1 (FEN1), a cellular factor recently identified to be involved in HR-mediated repair of stalled replication forks by actively inducing DSBs [ 171 ], hence restarting stalled replication forks in viral replication [ 172 ]. Furthermore, IE1 binds to p53 and inhibits p53’s inhibitory impact on Rad51, enabling HR [ 173 ]. Rad51 is a key regulator of HR, and its levels are much higher in HCMV-infected human foreskin fibroblasts (HFFs) [ 21 ], but not in normal cells [ 174 ].…”

Section: Hcmv Infection Affects Damage Repair Mechanisms During Ddrmentioning

confidence: 99%

DNA damage response(DDR): a link between cellular senescence and human cytomegalovirus

Wu,

Zhou,

Wang

et al. 2023

Virol J

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The DNA damage response (DDR) is a signaling cascade that is triggered by DNA damage, involving the halting of cell cycle progression and repair. It is a key event leading to senescence, which is characterized by irreversible cell cycle arrest and the senescence-associated secretory phenotype (SASP) that includes the expression of inflammatory cytokines. Human cytomegalovirus (HCMV) is a ubiquitous pathogen that plays an important role in the senescence process. It has been established that DDR is necessary for HCMV to replicate effectively. This paper reviews the relationship between DDR, cellular senescence, and HCMV, providing new sights for virus-induced senescence (VIS).

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“…89 The viral culture in HFFs has also been well documented, especially for the isolation and identification of mechanisms of the pathogenesis of cytomegalovirus in the cells. [90][91][92][93][94] HFFs have also been used to culture and study the varicella-zoster virus; 95,96 in the presence of a virus that has been implicated in the cytotoxic effects caused by enterovirus 97,98 by Coxsackie B virus type 1, 99,100 and evaluation of the mechanisms of infection and pathogenesis of herpes simplex virus type 1. 18,101 Human herpes virus 8 is associated with Kaposi's sarcoma 102 and Japanese encephalitis virus.…”

Section: Culture Of Hffs For the Diagnosis Of Pathogenic Microorganismsmentioning

confidence: 99%

Human foreskin fibroblasts: from waste bag to important biomedical applications

Oliveira

Costa

Marinho

et al. 2018

Journal of Clinical Urology

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Circumcision is one of the most performed surgical procedures worldwide, and it is estimated that one in three men worldwide is circumcised, which makes the preputial skin removed after surgery an abundant material for possible applications. In particular, it is possible efficiently to isolate the cells of the foreskin, with fibroblasts being the most abundant cells of the dermis and the most used in biomedical research. This work aimed to review the knowledge and obtain a broad view of the main applications of human foreskin fibroblast cell culture. A literature search was conducted, including clinical trials, preclinical basic research studies, reviews and experimental studies. Several medical and laboratory applications of human foreskin fibroblast cell culture have been described, especially when it comes to the use of human foreskin fibroblasts as feeder cells for the cultivation of human embryonic stem cells, in addition to co-culture with other cell types. The culture of foreskin fibroblasts has also been used to: obtain induced pluripotent stem cells; the diagnosis of Clostridium difficile; to test the toxicity and effect of substances on normal cells, especially the toxicity of possible antineoplastic drugs; in viral culture, mainly of the human cytomegalovirus, study of the pathogenesis of other microorganisms; varied studies of cellular physiology and cellular interactions. Fibroblasts are important for cell models for varied application cultures, demonstrating how the preputial material can be reused, making possible new applications. Level of evidence: Not applicable for this multicentre audit.

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Modulation of Homology-Directed Repair in T98G Glioblastoma Cells Due to Interactions between Wildtype p53, Rad51 and HCMV IE1-72

Cited by 6 publications

References 63 publications

Chromatin-Remodeling Factor SPOC1 Acts as a Cellular Restriction Factor against Human Cytomegalovirus by Repressing the Major Immediate Early Promoter

Chromatin-Remodeling Factor SPOC1 Acts as a Cellular Restriction Factor against Human Cytomegalovirus by Repressing the Major Immediate Early Promoter

DNA damage response(DDR): a link between cellular senescence and human cytomegalovirus

Human foreskin fibroblasts: from waste bag to important biomedical applications

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