Somatic mutation patterns at Ig and Non-Ig Loci
DNA Repair (Amst). 2023 Nov 28;133:103607. doi: 10.1016/j.dnarep.2023.103607. Online ahead of print.ABSTRACTThe reverse transcriptase (RT) model of immunoglobulin (Ig) somatic hypermutation (SHM) has received insufficient scientific attention. This is understandable given that DNA deamination mediated by activation-induced deaminase (AID), the initiating step of Ig SHM, has dominated experiments since 2002. We summarise some key history of the RT Ig SHM model dating to 1987. For example, it is now established that DNA polymerase η, the sole DNA repair polymerase involved in post-replication short-patch repair, is an effic...
Source: DNA Repair - December 6, 2023 Category: Genetics & Stem Cells Authors: Edward J Steele Andrew Franklin Robyn A Lindley Source Type: research
Potential cGAS-STING pathway functions in DNA damage responses, DNA replication and DNA repair
DNA Repair (Amst). 2023 Nov 30;133:103608. doi: 10.1016/j.dnarep.2023.103608. Online ahead of print.ABSTRACTThe major innate immune responder to the DNA of pathogens is the cyclic GMP-AMP (cGAMP) synthase (cGAS) - stimulator of interferon genes (STING) pathway. Most prominently, the outcome of cGAS signalling is the activation of inflammatory transcription through interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-kB). In addition, the cGAS-STING pathway can lead to the direct modulation of cellular processes independently of transcription, such as activation of autophagy. Under unperturbed conditions, se...
Source: DNA Repair - December 6, 2023 Category: Genetics & Stem Cells Authors: Christian Zierhut Source Type: research
Somatic mutation patterns at Ig and Non-Ig Loci
DNA Repair (Amst). 2023 Nov 28;133:103607. doi: 10.1016/j.dnarep.2023.103607. Online ahead of print.ABSTRACTThe reverse transcriptase (RT) model of immunoglobulin (Ig) somatic hypermutation (SHM) has received insufficient scientific attention. This is understandable given that DNA deamination mediated by activation-induced deaminase (AID), the initiating step of Ig SHM, has dominated experiments since 2002. We summarise some key history of the RT Ig SHM model dating to 1987. For example, it is now established that DNA polymerase η, the sole DNA repair polymerase involved in post-replication short-patch repair, is an effic...
Source: DNA Repair - December 6, 2023 Category: Genetics & Stem Cells Authors: Edward J Steele Andrew Franklin Robyn A Lindley Source Type: research
Potential cGAS-STING pathway functions in DNA damage responses, DNA replication and DNA repair
DNA Repair (Amst). 2023 Nov 30;133:103608. doi: 10.1016/j.dnarep.2023.103608. Online ahead of print.ABSTRACTThe major innate immune responder to the DNA of pathogens is the cyclic GMP-AMP (cGAMP) synthase (cGAS) - stimulator of interferon genes (STING) pathway. Most prominently, the outcome of cGAS signalling is the activation of inflammatory transcription through interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-kB). In addition, the cGAS-STING pathway can lead to the direct modulation of cellular processes independently of transcription, such as activation of autophagy. Under unperturbed conditions, se...
Source: DNA Repair - December 6, 2023 Category: Genetics & Stem Cells Authors: Christian Zierhut Source Type: research
Somatic mutation patterns at Ig and Non-Ig Loci
DNA Repair (Amst). 2023 Nov 28;133:103607. doi: 10.1016/j.dnarep.2023.103607. Online ahead of print.ABSTRACTThe reverse transcriptase (RT) model of immunoglobulin (Ig) somatic hypermutation (SHM) has received insufficient scientific attention. This is understandable given that DNA deamination mediated by activation-induced deaminase (AID), the initiating step of Ig SHM, has dominated experiments since 2002. We summarise some key history of the RT Ig SHM model dating to 1987. For example, it is now established that DNA polymerase η, the sole DNA repair polymerase involved in post-replication short-patch repair, is an effic...
Source: DNA Repair - December 6, 2023 Category: Genetics & Stem Cells Authors: Edward J Steele Andrew Franklin Robyn A Lindley Source Type: research
Potential cGAS-STING pathway functions in DNA damage responses, DNA replication and DNA repair
DNA Repair (Amst). 2023 Nov 30;133:103608. doi: 10.1016/j.dnarep.2023.103608. Online ahead of print.ABSTRACTThe major innate immune responder to the DNA of pathogens is the cyclic GMP-AMP (cGAMP) synthase (cGAS) - stimulator of interferon genes (STING) pathway. Most prominently, the outcome of cGAS signalling is the activation of inflammatory transcription through interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-kB). In addition, the cGAS-STING pathway can lead to the direct modulation of cellular processes independently of transcription, such as activation of autophagy. Under unperturbed conditions, se...
Source: DNA Repair - December 6, 2023 Category: Genetics & Stem Cells Authors: Christian Zierhut Source Type: research
A non-canonical nucleotide from viral genomes interferes with the oxidative DNA damage repair system
DNA Repair (Amst). 2023 Nov 20;133:103605. doi: 10.1016/j.dnarep.2023.103605. Online ahead of print.ABSTRACTOxidative damage is a major source of genomic instability in all organisms with the aerobic metabolism. 8-Oxoguanine (8-oxoG), an abundant oxidized purine, is mutagenic and must be controlled by a dedicated DNA repair system (GO system) that prevents G:C→T:A transversions through an easily formed 8-oxoG:A mispair. In some forms, the GO system is present in nearly all cellular organisms. However, recent studies uncovered many instances of viruses possessing non-canonical nucleotides in their genomes. The features of...
Source: DNA Repair - December 2, 2023 Category: Genetics & Stem Cells Authors: Anna V Yudkina Anton V Endutkin Evgeniia A Diatlova Dmitry O Zharkov Source Type: research
A non-canonical nucleotide from viral genomes interferes with the oxidative DNA damage repair system
DNA Repair (Amst). 2023 Nov 20;133:103605. doi: 10.1016/j.dnarep.2023.103605. Online ahead of print.ABSTRACTOxidative damage is a major source of genomic instability in all organisms with the aerobic metabolism. 8-Oxoguanine (8-oxoG), an abundant oxidized purine, is mutagenic and must be controlled by a dedicated DNA repair system (GO system) that prevents G:C→T:A transversions through an easily formed 8-oxoG:A mispair. In some forms, the GO system is present in nearly all cellular organisms. However, recent studies uncovered many instances of viruses possessing non-canonical nucleotides in their genomes. The features of...
Source: DNA Repair - December 2, 2023 Category: Genetics & Stem Cells Authors: Anna V Yudkina Anton V Endutkin Evgeniia A Diatlova Dmitry O Zharkov Source Type: research
A non-canonical nucleotide from viral genomes interferes with the oxidative DNA damage repair system
DNA Repair (Amst). 2023 Nov 20;133:103605. doi: 10.1016/j.dnarep.2023.103605. Online ahead of print.ABSTRACTOxidative damage is a major source of genomic instability in all organisms with the aerobic metabolism. 8-Oxoguanine (8-oxoG), an abundant oxidized purine, is mutagenic and must be controlled by a dedicated DNA repair system (GO system) that prevents G:C→T:A transversions through an easily formed 8-oxoG:A mispair. In some forms, the GO system is present in nearly all cellular organisms. However, recent studies uncovered many instances of viruses possessing non-canonical nucleotides in their genomes. The features of...
Source: DNA Repair - December 2, 2023 Category: Genetics & Stem Cells Authors: Anna V Yudkina Anton V Endutkin Evgeniia A Diatlova Dmitry O Zharkov Source Type: research
A non-canonical nucleotide from viral genomes interferes with the oxidative DNA damage repair system
DNA Repair (Amst). 2023 Nov 20;133:103605. doi: 10.1016/j.dnarep.2023.103605. Online ahead of print.ABSTRACTOxidative damage is a major source of genomic instability in all organisms with the aerobic metabolism. 8-Oxoguanine (8-oxoG), an abundant oxidized purine, is mutagenic and must be controlled by a dedicated DNA repair system (GO system) that prevents G:C→T:A transversions through an easily formed 8-oxoG:A mispair. In some forms, the GO system is present in nearly all cellular organisms. However, recent studies uncovered many instances of viruses possessing non-canonical nucleotides in their genomes. The features of...
Source: DNA Repair - December 2, 2023 Category: Genetics & Stem Cells Authors: Anna V Yudkina Anton V Endutkin Evgeniia A Diatlova Dmitry O Zharkov Source Type: research
Interaction of mitoxantrone with abasic sites - DNA strand cleavage and inhibition of apurinic/apyrimidinic endonuclease 1, APE1
In this study, mitoxantrone-mediated inhibition of APE1 at THF sites was shown to be consistent with preferential binding to, and thermal stabilization of DNA containing a THF site as compared to non-damaged DNA. Investigations into the properties of mitoxantrone at AP and 3' α,β-unsaturated aldehyde sites demonstrated that in addition to being a potent inhibitor of APE1 at these biologically-relevant substrates (∼ 0.5 μM IC50 on AP site-containing DNA), mitoxantrone also incised AP site-containing DNA by catalyzing β- and β/δ-elimination reactions. The efficiency of these reactions to generate the 3' α,β-unsatur...
Source: DNA Repair - December 1, 2023 Category: Genetics & Stem Cells Authors: Irina G Minko Samantha A Moellmer Michael M Luzadder Rachana Tomar Michael P Stone Amanda K McCullough R Stephen Lloyd Source Type: research
Interaction of mitoxantrone with abasic sites - DNA strand cleavage and inhibition of apurinic/apyrimidinic endonuclease 1, APE1
In this study, mitoxantrone-mediated inhibition of APE1 at THF sites was shown to be consistent with preferential binding to, and thermal stabilization of DNA containing a THF site as compared to non-damaged DNA. Investigations into the properties of mitoxantrone at AP and 3' α,β-unsaturated aldehyde sites demonstrated that in addition to being a potent inhibitor of APE1 at these biologically-relevant substrates (∼ 0.5 μM IC50 on AP site-containing DNA), mitoxantrone also incised AP site-containing DNA by catalyzing β- and β/δ-elimination reactions. The efficiency of these reactions to generate the 3' α,β-unsatur...
Source: DNA Repair - December 1, 2023 Category: Genetics & Stem Cells Authors: Irina G Minko Samantha A Moellmer Michael M Luzadder Rachana Tomar Michael P Stone Amanda K McCullough R Stephen Lloyd Source Type: research
FAM21 interacts with Ku to promote the localization of WASH to DNA double strand break sites
DNA Repair (Amst). 2023 Nov 18;133:103603. doi: 10.1016/j.dnarep.2023.103603. Online ahead of print.ABSTRACTCytoplasmic FAM21 works as a guiding protein in Wiskott-Aldrich Syndrome Protein and SCAR Homolog (WASH) complex by linking WASH complex to endosomes through its interaction with retromer. Recently, we have reported that nuclear WASH localizes to DNA double strand break (DSB) sites to promote DNA repair through non-homologous end-joining (NHEJ). However, whether FAM21, the close partner of WASH, is involved in the nuclear WASH localization and DNA repair remains to be clarified. Here, we show that FAM21 interacts wit...
Source: DNA Repair - November 29, 2023 Category: Genetics & Stem Cells Authors: Tao Wang Ai-Xue Zheng Ping Li Tuo Tang Lu-Ping Zhang Yu Hong Xian Hong Zhi-Hui Deng Source Type: research
Regulatory apoptotic fragment of PARP1 complements catalytic fragment for PAR and DNA-dependent activity but inhibits DNA-induced catalytic stimulation of PARP2
DNA Repair (Amst). 2023 Nov 15;133:103593. doi: 10.1016/j.dnarep.2023.103593. Online ahead of print.ABSTRACTTo maintain tissue homeostasis, cell proliferation is balanced by cell death. PARP1 is an important protein involved in both processes. Upon sensing DNA damage, PARP1 forms poly(ADP-ribose) (PAR) chains to recruit the repair proteins, ensuring genome integrity and faithful cell proliferation. In addition, PAR also regulates the activity of PARP1. Persistent DNA damage can signal the cell to progress toward programmed cell death, apoptosis. During apoptosis, proteolytic cleavage of PARP1 generates an N-terminal, ZnF1-...
Source: DNA Repair - November 29, 2023 Category: Genetics & Stem Cells Authors: Waghela Deeksha Eerappa Rajakumara Source Type: research
FAM21 interacts with Ku to promote the localization of WASH to DNA double strand break sites
DNA Repair (Amst). 2023 Nov 18;133:103603. doi: 10.1016/j.dnarep.2023.103603. Online ahead of print.ABSTRACTCytoplasmic FAM21 works as a guiding protein in Wiskott-Aldrich Syndrome Protein and SCAR Homolog (WASH) complex by linking WASH complex to endosomes through its interaction with retromer. Recently, we have reported that nuclear WASH localizes to DNA double strand break (DSB) sites to promote DNA repair through non-homologous end-joining (NHEJ). However, whether FAM21, the close partner of WASH, is involved in the nuclear WASH localization and DNA repair remains to be clarified. Here, we show that FAM21 interacts wit...
Source: DNA Repair - November 29, 2023 Category: Genetics & Stem Cells Authors: Tao Wang Ai-Xue Zheng Ping Li Tuo Tang Lu-Ping Zhang Yu Hong Xian Hong Zhi-Hui Deng Source Type: research
