DNA Repair: The Search for Homology

Haber, James E.

doi:10.1002/bies.201700229

Cited by 115 publications

(108 citation statements)

References 113 publications

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“…Moreover, a recent study has suggested that the underlying causes of these four biomarkers may differ. High TMB and MSI are caused by defects in the DNA damage repair system, which is composed of many proteins in addition to MMR components, including the homologous recombination repair element RecA/Rad51 and the non‐homologous end joining repair element Ku70/Ku80 . Research has shown that in the absence of MSI, mutations in DNA polymerase (POLE) can lead to TMB‐H .…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of potential immunotherapy genomic biomarkers in 1000 Chinese patients with cancer

Zang

Dai

et al. 2019

Cancer Medicine

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Background Tumor mutation burden (TMB), DNA mismatch repair deficiency (dMMR), microsatellite instability (MSI), and PD‐L1 amplification (PD‐L1 AMP) may predict the efficacy of the PD‐1/PD‐L1 blockade. With the broadening landscape of immunotherapy use, it is important to identify patients who are likely to benefit from the therapy. This study aimed to characterize the distributions of these biomarkers and explore the relationships among these biomarkers for Chinese patients with cancer. Methods In this study, we examined the aforementioned biomarkers in more than 1000 Chinese patients with cancer. These biomarkers were determined based on whole‐exome sequencing (WES) of tumor/blood samples. Results Of the 953 samples from Chinese cancer patients assessed in this study, 35% exhibited high TMB (TMB‐H), 4% were positive for high MSI (MSI‐H), dMMR occurred in 0.53%, and PD‐L1 AMP was positive in 3.79%. We found higher rates of TMB‐H among hepatocellular carcinoma, breast cancer, and esophageal cancer patients than was reported for The Cancer Genome Atlas (TCGA) data. Lung cancer patients with EGFR mutations had significantly lower TMB values than those with wild‐type EGFR , and increased TMB was significantly associated with dMMR in colorectal cancer (CRC). The frequency of tumors with MSI‐H was the highest in CRC and gastric cancer. PD‐L1 AMP occurred most frequently in lung squamous cell carcinoma and HER2‐positive breast cancer. While MSI and dMMR are associated with higher mutational loads, correlations between TMB‐H and other biomarkers, between MSI‐H and dMMR, and between PD‐L1 AMP and other biomarkers were low, indicating different underlying causes of the four biomarkers. Conclusion The results reveal the frequency of these biomarkers in different malignancies, with potential implications for PD‐1/PD‐L1 blockade use for Chinese patients with cancer.

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Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of potential immunotherapy genomic biomarkers in 1000 Chinese patients with cancer

Zang

Dai

et al. 2019

Cancer Medicine

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“…30 Shifts, which are not possible by replacing virus segments, may have occurred in coronavirus. Since it does not copy the genome into double-stranded DNA, RNA splicing in nucleus (18) or RNA interference would be used instead of the ordinal homologous recombination by the RecA family (19). Those may also be the cause of frequent indels.…”

Section: Discussionmentioning

confidence: 99%

Coronavirus, as a source of pandemic pathogens

Konishi

2020

Preprint

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The coronavirus and the influenza virus have similarities and differences. In order to comprehensively compare them, their genome sequencing data were examined by principal component analysis. Variations in coronavirus were smaller than those in a subclass of the influenza virus. In addition, differences among coronaviruses in a variety of hosts were small. These characteristics may have facilitated the infection of different hosts. Although many of the 10 coronaviruses were more conservative, those repeatedly found among humans showed annual changes. If SARS-CoV-2 changes its genome like the Influenza H type, it will repeatedly spread every few years. In addition, the coronavirus family has many other candidates for subsequent pandemics. One Sentence Summary:The genome data of coronavirus were compared to influenza virus, to 15 investigate its spreading mechanism and future status. Short titles: Coronavirus, as a source of pandemics.Main Text: COVID-19 (1, 2) is rapidly spreading worldwide. To investigate its spreading mechanism, genomes of the coronavirus were compared to those of the influenza virus (3) by principal component analysis (PCA) (4). These two RNA viruses differed in host specificity and 20 speed of mutations. Here, I present the characteristics of both and the changes in coronavirus. The coronaviruses presented smaller variations and did not differ much from host to host. These characteristics may have eased the novel transfection of coronaviruses to humans; many of the bat strains seem to have the ability to infect humans, and the intermediate animals may not be necessarily required, against the present expectations. Although many of the coronaviruses were 25

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“…HR is a high-fidelity DNA repair mechanism that functions to rejoin DSBs (37). HR, which occurs in the S or G2 phase of the cell cycle, uses a homologous DNA sequence as a template to guide the faithful repair of DSBs (38).…”

Section: Discussionmentioning

confidence: 99%

RMI1 contributes to DNA repair and to the tolerance to camptothecin

et al. 2019

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Maintenance of genome integrity is critical for faithful propagation of genetic information and the prevention of the mutagenesis induced by various DNA damage events. RecQ‐mediated genome instability protein 1 (RMI1), together with Bloom syndrome protein and topoisomerase IIIα, form an evolutionarily conserved complex that is critical for the maintenance of genomic stability. Herein, we report that RMI1 depletion increases cell sensitivity to camptothecin treatment, as shown by an elevation of genotoxic stress‐induced DNA double‐strand breaks, a stronger activation of the DNA damage response, and a greater G2/M cell cycle delay. Our findings support that, upon DNA damage, RMI1 forms nuclear foci at the damaged regions, interacts with RAD51, and facilitates the recruitment of RAD51 to initiate homologous recombination. Our data reveal the importance of RMI1 in response to DNA double‐strand breaks and shed light on the molecular mechanisms by which RMI1 contributes to maintain genome stability.—Fang, L., Sun, X., Wang, Y., Du, L., Ji, K., Wang, J., He, N., Liu, Y., Wang, Q., Zhai, H., Hao, J., Xu, C., Liu, Q. RMI1 contributes to DNA repair and to the tolerance to camptothecin. FASEB J. 33, 5561–5570 (2019). http://www.fasebj.org

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DNA Repair: The Search for Homology

Cited by 115 publications

References 113 publications

Comprehensive analysis of potential immunotherapy genomic biomarkers in 1000 Chinese patients with cancer

Comprehensive analysis of potential immunotherapy genomic biomarkers in 1000 Chinese patients with cancer

Coronavirus, as a source of pandemic pathogens

RMI1 contributes to DNA repair and to the tolerance to camptothecin

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