Role of DNA Repair Deficiency in Cancer Development

Alhegaili, Alaa Saud

doi:10.3923/pjbs.2023.15.22

Cited by 2 publications

(2 citation statements)

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“…In both bacteria and eukaryotes, genome instability increases when recombination genes are mutated [ 13 , 14 , 15 ]. Cancer cells that often display high levels of genome instability are replete with mutations in HR and other DNA damage repair genes [ 16 , 17 , 18 , 19 ]. In human cells, HR is facilitated primarily by the BRCA2-BRCA1-PALB2 module, which loads RAD51 onto a resected single-stranded end to initiate a homologous search and strand exchange [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

F-box DNA Helicase 1 (FBH1) Contributes to the Destabilization of DNA Damage Repair Machinery in Human Cancers

Watson,

Shaffer,

Bouley

et al. 2023

Cancers

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Homologous recombination (HR) is the major mechanism of rescue of stalled replication forks or repair of DNA double-strand breaks (DSBs) during S phase or mitosis. In human cells, HR is facilitated by the BRCA2-BRCA1-PALB2 module, which loads the RAD51 recombinase onto a resected single-stranded DNA end to initiate repair. Although the process is essential for error-free repair, unrestrained HR can cause chromosomal rearrangements and genome instability. F-box DNA Helicase 1 (FBH1) antagonizes the role of BRCA2-BRCA1-PALB2 to restrict hyper-recombination and prevent genome instability. Here, we analyzed reported FBH1 mutations in cancer cells using the Catalogue of Somatic Mutations in Cancers (COSMIC) to understand how they interact with the BRCA2-BRCA1-PALB2. Consistent with previous results from yeast, we find that FBH1 mutations co-occur with BRCA2 mutations and to some degree BRCA1 and PALB2. We also describe some co-occurring mutations with RAD52, the accessory RAD51 loader and facilitator of single-strand annealing, which is independent of RAD51. In silico modeling was used to investigate the role of key FBH1 mutations on protein function, and a Q650K mutation was found to destabilize the protein structure. Taken together, this work highlights how mutations in several DNA damage repair genes contribute to cellular transformation and immortalization.

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Section: Introductionmentioning

confidence: 99%

F-box DNA Helicase 1 (FBH1) Contributes to the Destabilization of DNA Damage Repair Machinery in Human Cancers

Watson,

Shaffer,

Bouley

et al. 2023

Cancers

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“…To achieve this, the DNA repair machinery promptly initiates corrective actions upon lesion detection, aiming to rectify altered bases or any other anomalies. In the literature, several well-defined DNA repair pathways exist, encompassing direct reversal, excision repair [including base excision repair (BER) and nucleotide excision repair (NER)], mismatch repair (MMR), and double-strand break (DSB) repair pathways [including homologous recombination repair (HR) and non-homologous end joining (NHEJ)] (12,13). Among these pathways, DSBs represent the most severe form of DNA damage, stemming from both endogenous and exogenous factors, such as replication errors, ionizing radiation exposure, free radicals, and telomere dysfunction (14,15).…”

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confidence: 99%

The Contribution of DNA Ligase 4 Polymorphisms to Colorectal Cancer

DENG,

KE,

YUEH

et al. 2023

In Vivo

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Background/Aim: While numerous biomarkers associated with genetic susceptibility to colorectal cancer (CRC) have been identified and validated through epidemiological studies, the specific influence of DNA ligase 4 (Lig4) genotypes remains unexplored. This study aimed to elucidate the hitherto unexamined relationship between Lig4 genotypes and CRC risk. Materials and Methods: The genotypes of Lig4 rs1805388 were determined applying the polymerase chain reaction-restriction fragment length polymorphism methodology. The potential association between these genotypes and CRC risk was assessed in a Taiwanese population comprising 362 CRC cases and an equal number of age-and sex-matched controls. Results: In the genotypic analysis, the distribution of CC, CT, and TT genotypes for Lig4 rs1805388 among CRC cases was 54.7%, 38.1%, and 7.2%, respectively. This distribution was not significantly different from the controls, which exhibited genotypic frequencies of 57.2%, 36.7%, and 6.1%, respectively (p for trend=0.7314). Analysis of allelic distribution indicated that individuals carrying the T allele of Lig4 rs1805388 displayed a slightly elevated CRC risk compared to those carrying the C allele (odds ratio=1.10, 95% confidence interval=0. 87-1.39, p=0.4685) . Conclusion:The variant genotypes of Lig4 rs1805388 may not serve as predictive markers for CRC risk in the Taiwanese population.Colorectal cancer (CRC) constitutes approximately 11% of all newly diagnosed cancer cases and stands as the third most prevalent cancer worldwide, leading to the second highest number of cancer-related fatalities (1). The pathogenesis of CRC encompasses a myriad of factors that contribute to intricate genetic and epigenetic mechanisms, culminating in the conversion of normal colonic mucosa into malignant tissues (2). Deficient DNA repair capacity is closely linked with genomic instability and heightened susceptibility to cancer (3-5). Furthermore, emerging evidence underscores the strong correlation between genetic variations in the DNA damage responses, microsatellite instability status and mitochondrial copy numbers and other pathways, serving as crucial determinants for CRC patients (6-11).

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Role of DNA Repair Deficiency in Cancer Development

Cited by 2 publications

References 50 publications

F-box DNA Helicase 1 (FBH1) Contributes to the Destabilization of DNA Damage Repair Machinery in Human Cancers

F-box DNA Helicase 1 (FBH1) Contributes to the Destabilization of DNA Damage Repair Machinery in Human Cancers

The Contribution of DNA Ligase 4 Polymorphisms to Colorectal Cancer

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