scholarly journals Tyrosine kinase c-Abl couples RNA polymerase II transcription to DNA double-strand breaks

2019 ◽  
Vol 47 (7) ◽  
pp. 3467-3484 ◽  
Author(s):  
Kaspar Burger ◽  
Margarita Schlackow ◽  
Monika Gullerova
Keyword(s):  
Tyrosine Kinase ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Kinase C ◽  
Rna Polymerase Ii Transcription

scholarly journals RNA polymerase II is recruited to DNA double-strand breaks for dilncRNA transcription in Drosophila

RNA Biology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Romy Böttcher ◽  
Ines Schmidts ◽  
Volker Nitschko ◽  
Petar Duric ◽  
Klaus Förstemann
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks

scholarly journals Splicing stimulates antisense transcription by RNA polymerase II at DNA double-strand breaks in Drosophila cells

2021 ◽  
Author(s):  
Romy Boettcher ◽  
Ines Schmidts ◽  
Volker Nitschko ◽  
Petar Duric ◽  
Klaus Foerstemann
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Rna Polymerase Iii ◽  
Selective Inhibition ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Polymerase Iii ◽  
A Genome ◽  
Nascent Rna

DNA double-strand breaks are among the most toxic lesions that can occur in a genome and their faithful repair is thus of great importance. Recent findings have uncovered a role for local transcription that initiates at the break and forms a non-coding transcript, called damage-induced long non-coding RNA or dilncRNA, which helps to coordinate the DNA transactions necessary for repair. We provide nascent RNA sequencing-based evidence that dilncRNA transcription by RNA polymerase II is more efficient if the DNA break occurs in an intron-containing gene in Drosophila. The spliceosome thus stimulates recruitment of RNA polymerase to the break, rather than the annealing of sense and antisense RNA. In contrast, RNA polymerase III nascent RNA libraries did not contain reads corresponding to the cleaved loci. Furthermore, selective inhibition of RNA polymerase III did not reduce the yield of damage-induced siRNAs (derived from the dilncRNA in Drosophila) and the damage-induced siRNA density was unchanged downstream of a T8 sequence, which terminates RNA polymerase III transcription. We thus found no evidence for a participation of RNA polymerase III in dilncRNA transcription and damage-induced siRNA generation in flies.

scholarly journals BCR-ABL promotes the frequency of mutagenic single-strand annealing DNA repair

Blood ◽  
2009 ◽  
Vol 114 (9) ◽  
pp. 1813-1819 ◽  
Author(s):  
Margret S. Fernandes ◽  
Mamatha M. Reddy ◽  
Jeffrey R. Gonneville ◽  
Scott C. DeRoo ◽  
Klaus Podar ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Double Strand Breaks ◽  
Single Strand ◽  
Model Systems ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Single Strand Annealing ◽  
Strand Annealing

Intracellular oxidative stress in cells transformed by the BCR-ABL oncogene is associated with increased DNA double-strand breaks. Imprecise repair of these breaks can result in the accumulation of mutations, leading to therapy-related drug resistance and disease progression. Using several BCR-ABL model systems, we found that BCR-ABL specifically promotes the repair of double-strand breaks through single-strand annealing (SSA), a mutagenic pathway that involves sequence repeats. Moreover, our results suggest that mutagenic SSA repair can be regulated through the interplay between BCR-ABL and extrinsic growth factors. Increased SSA activity required Y177 in BCR-ABL, as well as a functional PI3K and Ras pathway downstream of this site. Furthermore, our data hint at a common pathway for DSB repair whereby BCR-ABL, Tel-ABL, Tel-PDGFR, FLT3-ITD, and Jak2V617F all increase mutagenic repair. This increase in SSA may not be sufficiently suppressed by tyrosine kinase inhibitors in the stromal microenvironment. Therefore, drugs that target growth factor receptor signaling represent potential therapeutic agents to combat tyrosine kinase-induced genomic instability.

Repair pathway choice for double-strand breaks

2020 ◽  
Vol 64 (5) ◽  
pp. 765-777 ◽  
Author(s):  
Yixi Xu ◽  
Dongyi Xu
Keyword(s):  
Cell Cycle ◽  
Double Strand Breaks ◽  
Homologous Region ◽  
Gene Repair ◽  
Repair Pathway ◽  
Dna Double Strand Breaks ◽  
Environmental Radiation ◽  
Strand Breaks ◽  
Dna End Resection ◽  
End Resection

Abstract Deoxyribonucleic acid (DNA) is at a constant risk of damage from endogenous substances, environmental radiation, and chemical stressors. DNA double-strand breaks (DSBs) pose a significant threat to genomic integrity and cell survival. There are two major pathways for DSB repair: nonhomologous end-joining (NHEJ) and homologous recombination (HR). The extent of DNA end resection, which determines the length of the 3′ single-stranded DNA (ssDNA) overhang, is the primary factor that determines whether repair is carried out via NHEJ or HR. NHEJ, which does not require a 3′ ssDNA tail, occurs throughout the cell cycle. 53BP1 and the cofactors PTIP or RIF1-shieldin protect the broken DNA end, inhibit long-range end resection and thus promote NHEJ. In contrast, HR mainly occurs during the S/G2 phase and requires DNA end processing to create a 3′ tail that can invade a homologous region, ensuring faithful gene repair. BRCA1 and the cofactors CtIP, EXO1, BLM/DNA2, and the MRE11–RAD50–NBS1 (MRN) complex promote DNA end resection and thus HR. DNA resection is influenced by the cell cycle, the chromatin environment, and the complexity of the DNA end break. Herein, we summarize the key factors involved in repair pathway selection for DSBs and discuss recent related publications.

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