Impairment of the non-catalytic subunit Dpb2 of DNA Pol ɛ results in increased involvement of Pol δ on the leading strand
DNA Repair (Amst). 2023 Jul 7;129:103541. doi: 10.1016/j.dnarep.2023.103541. Online ahead of print.ABSTRACTThe generally accepted model assumes that leading strand synthesis is performed by Pol ε, while lagging-strand synthesis is catalyzed by Pol δ. Pol ε has been shown to target the leading strand by interacting with the CMG helicase [Cdc45 Mcm2-7 GINS(Psf1-3, Sld5)]. Proper functioning of the CMG-Pol ɛ, the helicase-polymerase complex is essential for its progression and the fidelity of DNA replication. Dpb2p, the essential non-catalytic subunit of Pol ε plays a key role in maintaining the correct architecture of t...
Source: DNA Repair - July 23, 2023 Category: Genetics & Stem Cells Authors: Michal Dmowski Karolina Makiela-Dzbenska Sushma Sharma Andrei Chabes Iwona J Fijalkowska Source Type: research
Impairment of the non-catalytic subunit Dpb2 of DNA Pol ɛ results in increased involvement of Pol δ on the leading strand
DNA Repair (Amst). 2023 Jul 7;129:103541. doi: 10.1016/j.dnarep.2023.103541. Online ahead of print.ABSTRACTThe generally accepted model assumes that leading strand synthesis is performed by Pol ε, while lagging-strand synthesis is catalyzed by Pol δ. Pol ε has been shown to target the leading strand by interacting with the CMG helicase [Cdc45 Mcm2-7 GINS(Psf1-3, Sld5)]. Proper functioning of the CMG-Pol ɛ, the helicase-polymerase complex is essential for its progression and the fidelity of DNA replication. Dpb2p, the essential non-catalytic subunit of Pol ε plays a key role in maintaining the correct architecture of t...
Source: DNA Repair - July 23, 2023 Category: Genetics & Stem Cells Authors: Michal Dmowski Karolina Makiela-Dzbenska Sushma Sharma Andrei Chabes Iwona J Fijalkowska Source Type: research
Phosphoregulation of the checkpoint kinase Mec1 < sup > ATR < /sup >
DNA Repair (Amst). 2023 Jul 17;129:103543. doi: 10.1016/j.dnarep.2023.103543. Online ahead of print.ABSTRACTYeast Mec1, and its mammalian ortholog, Ataxia-Telangiectasia and Rad3-related, are giant protein kinases central to replication stress and double strand DNA break repair. Mec1ATR, in complex with Ddc2ATRIP, is a 'sensor' of single stranded DNA, and phosphorylates numerous cell cycle and DNA repair factors to enforce cell cycle arrest and facilitate repair. Over the last several years, new techniques - particularly in structural biology - have provided molecular mechanisms for Mec1ATR function. It is becoming increas...
Source: DNA Repair - July 22, 2023 Category: Genetics & Stem Cells Authors: Luke A Yates Xiaodong Zhang Source Type: research
Single-molecule approaches for DNA damage detection and repair: A focus on Repair Assisted Damage Detection (RADD)
DNA Repair (Amst). 2023 Jul 5;129:103533. doi: 10.1016/j.dnarep.2023.103533. Online ahead of print.ABSTRACTThe human genome is continually exposed to various stressors, which can result in DNA damage, mutations, and diseases. Among the different types of DNA damage, single-strand lesions are commonly induced by external stressors and metabolic processes. Accurate detection and quantification of DNA damage are crucial for understanding repair mechanisms, assessing environmental impacts, and evaluating response to therapy. However, traditional techniques have limitations in sensitivity and the ability to detect multiple type...
Source: DNA Repair - July 19, 2023 Category: Genetics & Stem Cells Authors: Tahir Detinis Zur Jasline Deek Yuval Ebenstein Source Type: research
Synergistic effects on mutagenicity of tandem lesions containing 8-oxo-7,8-dihydro-2'-deoxyguanosine or Fapy •dG flanked by a 3' 5-formyl-2'-deoxyuridine in human cells
We examined the replication of 5'- 8-OxodGuo-5fdU and 5'-Fapy•dG-5fdU tandem lesions in HEK 293T cells and several polymerase deficient variants by transfecting single-stranded vectors containing them. The local sequence of the tandem lesions encompasses the 273 codon of the p53 gene, a mutational hot-spot. The bypass efficiency and mutation spectra of the tandem lesions were compared to those of the isolated lesions. Replication of weakly mutagenic 5-fdU is little changed when part of the 5'- 8-OxodGuo-5fdU tandem lesion. G → T transversions attributable to 8-OxodGuo increase > 10-fold when the tandem lesion is byp...
Source: DNA Repair - July 19, 2023 Category: Genetics & Stem Cells Authors: Jan Henric T Bacurio Shijun Gao Haozhe Yang Ashis K Basu Marc M Greenberg Source Type: research
Live cell single-molecule imaging to study DNA repair in human cells
DNA Repair (Amst). 2023 Jul 13;129:103540. doi: 10.1016/j.dnarep.2023.103540. Online ahead of print.ABSTRACTThe genetic material in human cells is continuously exposed to a wide variety of insults that can induce different DNA lesions. To maintain genomic stability and prevent potentially deleterious genetic changes caused by DNA damage, mammalian cells have evolved a number of pathways that repair specific types of DNA damage. These DNA repair pathways vary in their accuracy, some providing high-fidelity repair while others are error-prone and are only activated as a last resort. Adding additional complexity to cellular m...
Source: DNA Repair - July 19, 2023 Category: Genetics & Stem Cells Authors: Joshua R Heyza Mariia Mikhova Jens C Schmidt Source Type: research
Single-molecule approaches for DNA damage detection and repair: A focus on Repair Assisted Damage Detection (RADD)
DNA Repair (Amst). 2023 Jul 5;129:103533. doi: 10.1016/j.dnarep.2023.103533. Online ahead of print.ABSTRACTThe human genome is continually exposed to various stressors, which can result in DNA damage, mutations, and diseases. Among the different types of DNA damage, single-strand lesions are commonly induced by external stressors and metabolic processes. Accurate detection and quantification of DNA damage are crucial for understanding repair mechanisms, assessing environmental impacts, and evaluating response to therapy. However, traditional techniques have limitations in sensitivity and the ability to detect multiple type...
Source: DNA Repair - July 19, 2023 Category: Genetics & Stem Cells Authors: Tahir Detinis Zur Jasline Deek Yuval Ebenstein Source Type: research
Synergistic effects on mutagenicity of tandem lesions containing 8-oxo-7,8-dihydro-2'-deoxyguanosine or Fapy •dG flanked by a 3' 5-formyl-2'-deoxyuridine in human cells
We examined the replication of 5'- 8-OxodGuo-5fdU and 5'-Fapy•dG-5fdU tandem lesions in HEK 293T cells and several polymerase deficient variants by transfecting single-stranded vectors containing them. The local sequence of the tandem lesions encompasses the 273 codon of the p53 gene, a mutational hot-spot. The bypass efficiency and mutation spectra of the tandem lesions were compared to those of the isolated lesions. Replication of weakly mutagenic 5-fdU is little changed when part of the 5'- 8-OxodGuo-5fdU tandem lesion. G → T transversions attributable to 8-OxodGuo increase > 10-fold when the tandem lesion is byp...
Source: DNA Repair - July 19, 2023 Category: Genetics & Stem Cells Authors: Jan Henric T Bacurio Shijun Gao Haozhe Yang Ashis K Basu Marc M Greenberg Source Type: research
Live cell single-molecule imaging to study DNA repair in human cells
DNA Repair (Amst). 2023 Jul 13;129:103540. doi: 10.1016/j.dnarep.2023.103540. Online ahead of print.ABSTRACTThe genetic material in human cells is continuously exposed to a wide variety of insults that can induce different DNA lesions. To maintain genomic stability and prevent potentially deleterious genetic changes caused by DNA damage, mammalian cells have evolved a number of pathways that repair specific types of DNA damage. These DNA repair pathways vary in their accuracy, some providing high-fidelity repair while others are error-prone and are only activated as a last resort. Adding additional complexity to cellular m...
Source: DNA Repair - July 19, 2023 Category: Genetics & Stem Cells Authors: Joshua R Heyza Mariia Mikhova Jens C Schmidt Source Type: research
Single-molecule approaches for DNA damage detection and repair: A focus on Repair Assisted Damage Detection (RADD)
DNA Repair (Amst). 2023 Jul 5;129:103533. doi: 10.1016/j.dnarep.2023.103533. Online ahead of print.ABSTRACTThe human genome is continually exposed to various stressors, which can result in DNA damage, mutations, and diseases. Among the different types of DNA damage, single-strand lesions are commonly induced by external stressors and metabolic processes. Accurate detection and quantification of DNA damage are crucial for understanding repair mechanisms, assessing environmental impacts, and evaluating response to therapy. However, traditional techniques have limitations in sensitivity and the ability to detect multiple type...
Source: DNA Repair - July 19, 2023 Category: Genetics & Stem Cells Authors: Tahir Detinis Zur Jasline Deek Yuval Ebenstein Source Type: research
Synergistic effects on mutagenicity of tandem lesions containing 8-oxo-7,8-dihydro-2'-deoxyguanosine or Fapy •dG flanked by a 3' 5-formyl-2'-deoxyuridine in human cells
We examined the replication of 5'- 8-OxodGuo-5fdU and 5'-Fapy•dG-5fdU tandem lesions in HEK 293T cells and several polymerase deficient variants by transfecting single-stranded vectors containing them. The local sequence of the tandem lesions encompasses the 273 codon of the p53 gene, a mutational hot-spot. The bypass efficiency and mutation spectra of the tandem lesions were compared to those of the isolated lesions. Replication of weakly mutagenic 5-fdU is little changed when part of the 5'- 8-OxodGuo-5fdU tandem lesion. G → T transversions attributable to 8-OxodGuo increase > 10-fold when the tandem lesion is byp...
Source: DNA Repair - July 19, 2023 Category: Genetics & Stem Cells Authors: Jan Henric T Bacurio Shijun Gao Haozhe Yang Ashis K Basu Marc M Greenberg Source Type: research
Live cell single-molecule imaging to study DNA repair in human cells
DNA Repair (Amst). 2023 Jul 13;129:103540. doi: 10.1016/j.dnarep.2023.103540. Online ahead of print.ABSTRACTThe genetic material in human cells is continuously exposed to a wide variety of insults that can induce different DNA lesions. To maintain genomic stability and prevent potentially deleterious genetic changes caused by DNA damage, mammalian cells have evolved a number of pathways that repair specific types of DNA damage. These DNA repair pathways vary in their accuracy, some providing high-fidelity repair while others are error-prone and are only activated as a last resort. Adding additional complexity to cellular m...
Source: DNA Repair - July 19, 2023 Category: Genetics & Stem Cells Authors: Joshua R Heyza Mariia Mikhova Jens C Schmidt Source Type: research
Single-molecule approaches for DNA damage detection and repair: A focus on Repair Assisted Damage Detection (RADD)
DNA Repair (Amst). 2023 Jul 5;129:103533. doi: 10.1016/j.dnarep.2023.103533. Online ahead of print.ABSTRACTThe human genome is continually exposed to various stressors, which can result in DNA damage, mutations, and diseases. Among the different types of DNA damage, single-strand lesions are commonly induced by external stressors and metabolic processes. Accurate detection and quantification of DNA damage are crucial for understanding repair mechanisms, assessing environmental impacts, and evaluating response to therapy. However, traditional techniques have limitations in sensitivity and the ability to detect multiple type...
Source: DNA Repair - July 19, 2023 Category: Genetics & Stem Cells Authors: Tahir Detinis Zur Jasline Deek Yuval Ebenstein Source Type: research
Synergistic effects on mutagenicity of tandem lesions containing 8-oxo-7,8-dihydro-2'-deoxyguanosine or Fapy •dG flanked by a 3' 5-formyl-2'-deoxyuridine in human cells
We examined the replication of 5'- 8-OxodGuo-5fdU and 5'-Fapy•dG-5fdU tandem lesions in HEK 293T cells and several polymerase deficient variants by transfecting single-stranded vectors containing them. The local sequence of the tandem lesions encompasses the 273 codon of the p53 gene, a mutational hot-spot. The bypass efficiency and mutation spectra of the tandem lesions were compared to those of the isolated lesions. Replication of weakly mutagenic 5-fdU is little changed when part of the 5'- 8-OxodGuo-5fdU tandem lesion. G → T transversions attributable to 8-OxodGuo increase > 10-fold when the tandem lesion is byp...
Source: DNA Repair - July 19, 2023 Category: Genetics & Stem Cells Authors: Jan Henric T Bacurio Shijun Gao Haozhe Yang Ashis K Basu Marc M Greenberg Source Type: research
Live cell single-molecule imaging to study DNA repair in human cells
DNA Repair (Amst). 2023 Jul 13;129:103540. doi: 10.1016/j.dnarep.2023.103540. Online ahead of print.ABSTRACTThe genetic material in human cells is continuously exposed to a wide variety of insults that can induce different DNA lesions. To maintain genomic stability and prevent potentially deleterious genetic changes caused by DNA damage, mammalian cells have evolved a number of pathways that repair specific types of DNA damage. These DNA repair pathways vary in their accuracy, some providing high-fidelity repair while others are error-prone and are only activated as a last resort. Adding additional complexity to cellular m...
Source: DNA Repair - July 19, 2023 Category: Genetics & Stem Cells Authors: Joshua R Heyza Mariia Mikhova Jens C Schmidt Source Type: research
