DNA Repair Pathways in Cancer Therapy and Resistance

Li, Lan-ya; Guan, Yifu; Chen, Xisha; Yang, Jin‐Ming; Cheng, Yan

doi:10.3389/fphar.2020.629266

Cited by 191 publications

(143 citation statements)

References 138 publications

(116 reference statements)

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“…The functioning of the eukaryotic genome relies on effective and accurate DNA replication and repair [2]. DNA replication in the nucleus of eukaryotic cells employs DNA polymerases (pols) α, β, δ, and ϵ, that are the key enzymes required to maintain the integrity of the genome under all these circumstances [1,3].…”

Section: P53 and Dna Repair In Nucleusmentioning

confidence: 99%

“…Humans are persistently exposed to various chemical and physical agents that have the potential to damage genomic DNA, such as, irradiation (IR), ultraviolet (UV) light, reactive oxygen species (ROS), et cetera [1]. The integrity and survival of a cell is critically dependent on genome stability and mammalian cells have established multiple pathways to repair different types of target DNA lesions to safeguard the genome from deleterious consequences of various kinds of stresses [2]. The significance of the DNA repair in the protection of genomic stability is highlighted by the fact that many proteins/factors involved have been preserved through evolution [3].…”

Section: Introductionmentioning

confidence: 99%

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The Role p53 Protein in DNA Repair

Bakhanashvili¹

2022

P53 - A Guardian of the Genome and Beyond

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The tumor suppressor p53 protein controls cell cycle and plays a vital role in preserving DNA integrity. p53 is activated by varied stress signals and the distribution of p53 between the different subcellular compartments depends on the cellular stress milieu. DNA repair pathways protect cells from damage that can lead to DNA breaks. The multi-functional p53 protein promotes DNA repair both directly and indirectly through multiple mechanisms; it accomplishes multi-compartmental functions by either numerous p53-controlled proteins or by its inherent biochemical activities. Accumulating evidence supports the contribution of p53 in the maintenance of the genomic integrity and in various steps of the DNA damage response, through its translocation into nucleus and mitochondria. p53 may also be utilized by viral polymerases in cytoplasm to maintain genomic integrity of viruses, thus expanding the role of p53 as a ‘guardian of the genome’. We summarize recent findings highlighting roles of p53 in DNA repair.

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Section: P53 and Dna Repair In Nucleusmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Role p53 Protein in DNA Repair

Bakhanashvili¹

2022

P53 - A Guardian of the Genome and Beyond

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“…These results further support the idea that targeting kinase-independent functions of RAF1 open new avenues for anticancer therapy, e.g., by enhancing apoptosis inflicted by DNA damaging agents. Despite the headlines made by targeted therapies, DNA damaging chemotherapy is still the mainstay of cancer treatment and augmenting its efficacy could reduce side effects and increase responses [64].…”

Section: Raf Kinase-independent Regulation Of Cell Cycle and Mitosis Checkpointsmentioning

confidence: 99%

Hidden Targets in RAF Signalling Pathways to Block Oncogenic RAS Signalling

Nolan

Aboud

Kölch

et al. 2021

Genes

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Oncogenic RAS (Rat sarcoma) mutations drive more than half of human cancers, and RAS inhibition is the holy grail of oncology. Thirty years of relentless efforts and harsh disappointments have taught us about the intricacies of oncogenic RAS signalling that allow us to now get a pharmacological grip on this elusive protein. The inhibition of effector pathways, such as the RAF-MEK-ERK pathway, has largely proven disappointing. Thus far, most of these efforts were aimed at blocking the activation of ERK. Here, we discuss RAF-dependent pathways that are regulated through RAF functions independent of catalytic activity and their potential role as targets to block oncogenic RAS signalling. We focus on the now well documented roles of RAF kinase-independent functions in apoptosis, cell cycle progression and cell migration.

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“…Since abnormal function of DNA repair pathways is associated with the initiation and progression of cancer [53], further research should be conducted on the influence of alternative splice variants of XP genes on cancer risk. If a correlation between certain splice variants and cancer risk could be verified, these findings could be used to establish a marker panel to determine the individual cancer risk.…”

Section: Splice Variants Of Xeroderma Pigmentosum Genesmentioning

confidence: 99%

Xeroderma Pigmentosum: Gene Variants and Splice Variants

Martens

Emmert

Boeckmann

2021

Genes

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The nucleotide excision repair (NER) is essential for the repair of ultraviolet (UV)-induced DNA damage, such as cyclobutane pyrimidine dimers (CPDs) and 6,4-pyrimidine-pyrimidone dimers (6,4-PPs). Alterations in genes of the NER can lead to DNA damage repair disorders such as Xeroderma pigmentosum (XP). XP is a rare autosomal recessive genetic disorder associated with UV-sensitivity and early onset of skin cancer. Recently, extensive research has been conducted on the functional relevance of splice variants and their relation to cancer. Here, we focus on the functional relevance of alternative splice variants of XP genes.

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DNA Repair Pathways in Cancer Therapy and Resistance

Cited by 191 publications

References 138 publications

The Role p53 Protein in DNA Repair

The Role p53 Protein in DNA Repair

Hidden Targets in RAF Signalling Pathways to Block Oncogenic RAS Signalling

Xeroderma Pigmentosum: Gene Variants and Splice Variants

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