VE-822, a novel DNA Holliday junction stabilizer, inhibits homologous recombination repair and triggers DNA damage response in osteogenic sarcomas

2021 ◽  
pp. 114767
Author(s):  
Qikun Yin ◽  
Xuecun Liu ◽  
Lei Hu ◽  
Qinqin Song ◽  
Shuqi Liu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Homologous Recombination ◽  
Dna Damage Response ◽  
Holliday Junction ◽  
Homologous Recombination Repair ◽  
Recombination Repair ◽  
Damage Response

scholarly journals Regulation of DNA Damage Response and Homologous Recombination Repair by microRNA in Human Cells Exposed to Ionizing Radiation

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1838
Author(s):  
Magdalena Szatkowska ◽  
Renata Krupa
Keyword(s):  
Dna Damage ◽  
Homologous Recombination ◽  
Ionizing Radiation ◽  
Dna Damage Response ◽  
Cell Response ◽  
Dna Lesions ◽  
Homologous Recombination Repair ◽  
Recombination Repair ◽  
Damage Response ◽  
Radiation Induced

Ionizing radiation may be of both artificial and natural origin and causes cellular damage in living organisms. Radioactive isotopes have been used significantly in cancer therapy for many years. The formation of DNA double-strand breaks (DSBs) is the most dangerous effect of ionizing radiation on the cellular level. After irradiation, cells activate a DNA damage response, the molecular path that determines the fate of the cell. As an important element of this, homologous recombination repair is a crucial pathway for the error-free repair of DNA lesions. All components of DNA damage response are regulated by specific microRNAs. MicroRNAs are single-stranded short noncoding RNAs of 20–25 nt in length. They are directly involved in the regulation of gene expression by repressing translation or by cleaving target mRNA. In the present review, we analyze the biological mechanisms by which miRNAs regulate cell response to ionizing radiation-induced double-stranded breaks with an emphasis on DNA repair by homologous recombination, and its main component, the RAD51 recombinase. On the other hand, we discuss the ability of DNA damage response proteins to launch particular miRNA expression and modulate the course of this process. A full understanding of cell response processes to radiation-induced DNA damage will allow us to develop new and more effective methods of ionizing radiation therapy for cancers, and may help to develop methods for preventing the harmful effects of ionizing radiation on healthy organisms.

AtMMS21 regulates DNA damage response and homologous recombination repair in Arabidopsis

DNA Repair ◽  
2014 ◽  
Vol 21 ◽  
pp. 140-147 ◽  
Author(s):  
Dongke Yuan ◽  
Jianbin Lai ◽  
Panglian Xu ◽  
Shengchun Zhang ◽  
Juanjuan Zhang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Homologous Recombination ◽  
Dna Damage Response ◽  
Homologous Recombination Repair ◽  
Recombination Repair ◽  
Damage Response

scholarly journals DICER-dependent biogenesis of let-7 miRNAs affects human cell response to DNA damage via targeting p21/p27

2015 ◽  
Vol 43 (3) ◽  
pp. 1626-1636 ◽  
Author(s):  
Bailong Liu ◽  
Min Liu ◽  
Jian Wang ◽  
Xiangming Zhang ◽  
Xiang Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Cell Response ◽  
Small Rnas ◽  
Mirna Biogenesis ◽  
Homologous Recombination Repair ◽  
Cell Resistance ◽  
Recombination Repair ◽  
Damage Response

Abstract Recently, it was reported that knockdown of DICER reduced the ATM-dependent DNA damage response and homologous recombination repair (HRR) via decreasing DICER-generated small RNAs at the damage sites. However, we found that knockdown of DICER dramatically increased cell resistance to camptothecin that induced damage required ATM to facilitate HRR. This phenotype is due to a prolonged G1/S transition via decreasing DICER-dependent biogenesis of miRNA let-7, which increased the p21Waf1/Cip1/p27Kip1 levels and resulted in decreasing the HRR efficiency. These results uncover a novel function of DICER in regulating the cell cycle through miRNA biogenesis, thus affecting cell response to DNA damage.

Association of Homologous Recombination-DNA Damage Response Gene Mutations with Immune Biomarkers in Gastroesophageal Cancers

2021 ◽  
pp. molcanther.0879.2020
Author(s):  
Michael Cerniglia ◽  
Joanne Xiu ◽  
Axel Grothey ◽  
Michael J Pishvaian ◽  
Yasmine Baca ◽  
...  
Keyword(s):  
Dna Damage ◽  
Homologous Recombination ◽  
Dna Damage Response ◽  
Gene Mutations ◽  
Response Gene ◽  
Immune Biomarkers ◽  
Damage Response

scholarly journals Biphasic recruitment of TRF2 to DNA damage sites promotes non-sister chromatid homologous recombination repair

2018 ◽  
Vol 131 (23) ◽  
pp. jcs219311 ◽  
Author(s):  
Xiangduo Kong ◽  
Gladys Mae Saquilabon Cruz ◽  
Sally Loyal Trinh ◽  
Xu-Dong Zhu ◽  
Michael W. Berns ◽  
...  
Keyword(s):  
Dna Damage ◽  
Homologous Recombination ◽  
Sister Chromatid ◽  
Homologous Recombination Repair ◽  
Recombination Repair

scholarly journals Schizosaccharomyces pombe KAT5 contributes to resection and repair of a DNA double strand break

Genetics ◽  
2021 ◽  
Author(s):  
Tingting Li ◽  
Ruben C Petreaca ◽  
Susan L Forsburg
Keyword(s):  
Dna Damage ◽  
Homologous Recombination ◽  
Chromatin Remodeling ◽  
Dna Damage Response ◽  
Histone Acetyltransferase ◽  
Strand Break ◽  
Double Strand Break ◽  
Dna Damage Checkpoint ◽  
Dna Double Strand Break ◽  
Damage Response

Abstract Chromatin remodeling is essential for effective repair of a DNA double strand break. KAT5 (S. pombe Mst1, human TIP60) is a MYST family histone acetyltransferase conserved from yeast to humans that coordinates various DNA damage response activities at a DNA double strand break (DSB), including histone remodeling and activation of the DNA damage checkpoint. In S. pombe, mutations in mst1+ causes sensitivity to DNA damaging drugs. Here we show that Mst1 is recruited to DSBs. Mutation of mst1+ disrupts recruitment of repair proteins and delays resection. These defects are partially rescued by deletion of pku70, which has been previously shown to antagonize repair by homologous recombination. These phenotypes of mst1 are similar to pht1-4KR, a non-acetylatable form of histone variant H2A.Z, which has been proposed to affect resection. Our data suggest that Mst1 functions to direct repair of DSBs towards homologous recombination pathways by modulating resection at the double strand break.

scholarly journals PARP1-dependent recruitment of the FBXL10-RNF68-RNF2 ubiquitin ligase to sites of DNA damage controls H2A.Z loading

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Gergely Rona ◽  
Domenico Roberti ◽  
Yandong Yin ◽  
Julia K Pagan ◽  
Harrison Homer ◽  
...  
Keyword(s):  
Dna Damage ◽  
Homologous Recombination ◽  
Ubiquitin Ligase ◽  
Transcriptional Repression ◽  
Genotoxic Stress ◽  
Strand Break ◽  
Homologous Recombination Repair ◽  
Dependent Manner ◽  
Ubiquitin Ligase Complex ◽  
Recombination Repair

The mammalian FBXL10-RNF68-RNF2 ubiquitin ligase complex (FRRUC) mono-ubiquitylates H2A at Lys119 to repress transcription in unstressed cells. We found that the FRRUC is rapidly and transiently recruited to sites of DNA damage in a PARP1- and TIMELESS-dependent manner to promote mono-ubiquitylation of H2A at Lys119, a local decrease of H2A levels, and an increase of H2A.Z incorporation. Both the FRRUC and H2A.Z promote transcriptional repression, double strand break signaling, and homologous recombination repair (HRR). All these events require both the presence and activity of the FRRUC. Moreover, the FRRUC and its activity are required for the proper recruitment of BMI1-RNF2 and MEL18-RNF2, two other ubiquitin ligases that mono-ubiquitylate Lys119 in H2A upon genotoxic stress. Notably, whereas H2A.Z is not required for H2A mono-ubiquitylation, impairment of the latter results in the inhibition of H2A.Z incorporation. We propose that the recruitment of the FRRUC represents an early and critical regulatory step in HRR.

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