Role of Rad51 and DNA repair in cancer: A molecular perspective

Laurini, Erik; Marson, Domenico; Fermeglia, Alice; Aulić, Suzana; Fermeglia, Maurizio; Pricl, Sabrina

doi:10.1016/j.pharmthera.2020.107492

Cited by 82 publications

(84 citation statements)

References 647 publications

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“…Misregulation of RAD51, or one of its regulators, is associated with cancer as well as Fanconi anemia (FA)-like syndrome ( 6 , 7 ). While loss or reduction of RAD51 protein function can increase cancer risk, RAD51 upregulation in cancer can also contribute to therapeutic resistance ( 8 , 9 ). Maintaining appropriate levels of RAD51 expression and activity is critical for HR and thus cancer prevention.…”

Section: Introductionmentioning

confidence: 99%

Regulation and pharmacological targeting of RAD51 in cancer

2020

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Regulation of homologous recombination (HR) is central for cancer prevention. However, too little HR can increase cancer incidence, whereas too much HR can drive cancer resistance to therapy. Importantly, therapeutics targeting HR deficiency have demonstrated a profound efficacy in the clinic improving patient outcomes, particularly for breast and ovarian cancer. RAD51 is central to DNA damage repair in the HR pathway. As such, understanding the function and regulation of RAD51 is essential for cancer biology. This review will focus on the role of RAD51 in cancer and beyond and how modulation of its function can be exploited as a cancer therapeutic.

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Section: Introductionmentioning

confidence: 99%

Regulation and pharmacological targeting of RAD51 in cancer

2020

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“…RAD51 is another key protein in the HR pathway that is also associated with prognosis and treatment response in various cancers. A growing number of studies demonstrate that RAD51 protein is overexpressed in many cancers including breast, prostate, bladder, pancreas, and lung, and this overexpression can up-regulate HR activity and result in resistance to DNA-damaging drugs [88][89][90][91]. Increased expression of RAD51 has also been reported in sarcoma patients [92,93].…”

Section: Rad51mentioning

confidence: 99%

DNA Repair Defects in Sarcomas

Riyahi¹,

Saadatzadeh²,

Bijangi-Vishehsaraei³

et al. 2021

DNA - Damages and Repair Mechanisms

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DNA repair pathway is considered to be one of the most important mechanisms that protect cells from intrinsic and extrinsic stresses. It has been established that DNA repair activity has a crucial role in the way that cancer cells respond to treatment. Sarcomas are a group of tumors with mesenchymal origin in which their association with DNA repair aberrations has been reported in numerous studies. Special attention has been focused on exploiting these alterations to improve the patient’s overall survival and overcome drug resistance in cancer. While there is a large degree of heterogeneity among different types of sarcomas, DNA repair alteration is found to be a common defect in the majority of patients. In this chapter, we will introduce and review some of the most important dysregulated components involved in the DNA repair system, and discuss their association with tumorigenesis, cancer aggressiveness, drug resistance, and overall prognosis in the patients with sarcomas.

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“…In terms of mechanism, cells activate DNA damage response (DDR) to safeguard genomic integrity in response to DNA damage. The DDR consists of six major DNA repair pathways 11 . Two of these pathways, non‐homologous end joining (NHEJ) and homologous recombination (HR), dominate the repair of double‐strand breaks (DSBs) 12 .…”

Section: Introductionmentioning

confidence: 99%

“…NHEJ directly ligates the broken DNA ends, which is considered to be error‐prone 13 . By contrast, HR is an error free pathway that uses the information stored in a sister chromatin or homologue to repair the damage 11 . More importantly, HR is the most effective pathway activated in tumor cells to perform DSBs repair induced by Cis 14,15 .…”

Section: Introductionmentioning

confidence: 99%

Xanthatin synergizes with cisplatin to suppress homologous recombination through JAK2/STAT4/BARD1 axis in human NSCLC cells

Zhang

Yang

Guan

et al. 2021

J Cellular Molecular Medi

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Xanthatin (Xa) is a bicyclic sesquiterpene lactone identified from the plant Xanthium L . with impressive antitumor activity, but the role of Xa in non‐small cell lung cancer (NSCLC) is not known. Here we found that Xa inhibits proliferation, migration, invasion and induces apoptosis in NSCLC cells. RNA sequencing and Gene set enrichment analysis revealed that Xa significantly activates p53 pathway and suppresses E2F targets, G2M checkpoint and MYC targets in A549 cells. Among these changed genes, the down‐regulated gene BARD1 triggered by Xa was identified as a candidate involved in Xa’s antitumor effect because of its vital role in homologous recombination (HR). Further studies demonstrated that Xa inhibits HR through the BARD1/BRCA1/RAD51 axis, which enhances cell sensitivity to cisplatin. Mechanistic studies showed that Xa inhibits BARD1 through the JAK2/STAT4 pathway. Our study revealed that Xa is a promising drug to treat NSCLC, especially in combination with conventional chemotherapy.

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Role of Rad51 and DNA repair in cancer: A molecular perspective

Cited by 82 publications

References 647 publications

Regulation and pharmacological targeting of RAD51 in cancer

Regulation and pharmacological targeting of RAD51 in cancer

DNA Repair Defects in Sarcomas

Xanthatin synergizes with cisplatin to suppress homologous recombination through JAK2/STAT4/BARD1 axis in human NSCLC cells

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