Read by QxMD icon Read

DNA ligase

Alex Pines, Madelon Dijk, Matthew Makowski, Elisabeth M Meulenbroek, Mischa G Vrouwe, Yana van der Weegen, Marijke Baltissen, Pim J French, Martin E van Royen, Martijn S Luijsterburg, Leon H Mullenders, Michiel Vermeulen, Wim Vermeulen, Navraj S Pannu, Haico van Attikum
Transcription-blocking DNA lesions are removed by transcription-coupled nucleotide excision repair (TC-NER) to preserve cell viability. TC-NER is triggered by the stalling of RNA polymerase II at DNA lesions, leading to the recruitment of TC-NER-specific factors such as the CSA-DDB1-CUL4A-RBX1 cullin-RING ubiquitin ligase complex (CRLCSA ). Despite its vital role in TC-NER, little is known about the regulation of the CRLCSA complex during TC-NER. Using conventional and cross-linking immunoprecipitations coupled to mass spectrometry, we uncover a stable interaction between CSA and the TRiC chaperonin...
March 12, 2018: Nature Communications
Hok Khim Fam, Kunho Choi, Lauren Fougner, Chinten James Lim, Cornelius F Boerkoel
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a nuclear and mitochondrial protein that in nuclei and in vitro repairs blocked 3' DNA termini such as 3' phosphotyrosine conjugates resulting from stalling of topoisomerase I-DNA intermediates. Its mutation also causes spinocerebellar ataxia with axonal neuropathy type 1 (SCAN1). Because Tdp1 colocalizes with mitochondria following oxidative stress, we hypothesized that Tdp1 repairs mitochondrial DNA (mtDNA) and that mtDNA damage mediates entry of Tdp1 into the mitochondria...
March 9, 2018: Scientific Reports
Terrence Hanscom, Varandt Y Khodaverdian, Mitch McVey
In this chapter, we describe a method for the recovery and analysis of alternative end-joining (alt-EJ) DNA double-strand break repair junctions following I-SceI cutting in Drosophila melanogaster embryos. Alt-EJ can be defined as a set of Ku70/80 and DNA ligase 4-independent end-joining processes that are typically mutagenic, producing deletions, insertions, and chromosomal rearrangements more frequently than higher-fidelity repair pathways such as classical nonhomologous end joining or homologous recombination...
2018: Methods in Enzymology
Kang-Yi Su, Liang-In Lin, Steven D Goodman, Rong-Syuan Yen, Cho-Yuan Wu, Wei-Chen Chang, Ya-Chien Yang, Wern-Cherng Cheng, Woei-Horng Fang
Deamination of adenine can occur spontaneously under physiological conditions to generate the highly mutagenic lesion, deoxyinosine (hypoxanthine deoxyribonucleotide, dI). In DNA, dI preferably pairs with cytosine rather than thymine and results in A:T to G:C transition mutations after DNA replication. The deamination of adenine is enhanced by ROS from exposure of DNA to ionizing radiation, UV light, nitrous acid, or heat. In Escherichia coli, dI repair is initiated by endonuclease V (endo V; nfi gene product) nicking but a complete repair mechanism has yet to be elucidated...
February 17, 2018: DNA Repair
Wanxin Li, Song Zhang, Xiaoyun Wang, Jing Yu, Zeqi Li, Wenxiong Lin, Xiangmin Lin
Many antibiotics are used to kill pathogenic Escherichia coli each year, resulting in an increase in the number of antibiotic-resistant strains. In this study, an integrated metabonomic-proteomic method was performed to systematically compare the profiles of metabolites and proteins with or without ciprofloxacin (CFLX) treatment. Proteomics identified 290 altered proteins including 143 with decreased and 147 increased expression, respectively. Metabonomics identified 65 altered metabolites including 58 and 7 with decreased and increased expression, respectively...
March 6, 2018: Journal of Proteomics
Geetha S Hewawasam, Karthik Dhatchinamoorthy, Mark Mattingly, Chris Seidel, Jennifer L Gerton
Correct localization of the centromeric histone variant CenH3/CENP-A/Cse4 is an important part of faithful chromosome segregation. Mislocalization of CenH3 could affect chromosome segregation, DNA replication and transcription. CENP-A is often overexpressed and mislocalized in cancer genomes, but the underlying mechanisms are not understood. One major regulator of Cse4 deposition is Psh1, an E3 ubiquitin ligase that controls levels of Cse4 to prevent deposition into non-centromeric regions. We present evidence that Chromatin assembly factor-1 (CAF-1), an evolutionarily conserved histone H3/H4 chaperone with subunits shown previously to interact with CenH3 in flies and human cells, regulates Cse4 deposition in budding yeast...
March 7, 2018: Nucleic Acids Research
E A Belousova, А A Ishchenko, O I Lavrik
Most members of the poly(ADP-ribose)polymerase family, PARP family, have a catalytic activity that involves the transfer of ADP-ribose from a beta-NAD+-molecule to protein acceptors. It was recently discovered by Talhaoui et al. that DNA-dependent PARP1 and PARP2 can also modify DNA. Here, we demonstrate that DNA-dependent PARP3 can modify DNA and form a specific primed structure for further use by the repair proteins. We demonstrated that gapped DNA that was ADP-ribosylated by PARP3 could be ligated to double-stranded DNA by DNA ligases...
March 8, 2018: Scientific Reports
Wesley O Tucker, Andrew B Kinghorn, Lewis A Fraser, Yee-Wai Cheung, Julian A Tanner
Nucleic acid aptamers hold promise as therapeutic tools for specific, tailored inhibition of protein targets with several advantages when compared to small molecules or antibodies. Nuclear WW domain containing E3 ubiquitin ligase 1 (WWP1) ubiquitin ligase poly-ubiquitinates Runt-related transcription factor 2 (Runx2), a key transcription factor associated with osteoblast differentiation. Since WWP1 and an adapter known as Schnurri-3 are negative regulators of osteoblast function, the disruption of this complex has the potential to increase bone deposition for osteoporosis therapy...
March 7, 2018: International Journal of Molecular Sciences
Ja-Hyun Koo, Heeseok Yoon, Won-Ju Kim, Donghun Cha, Je-Min Choi
Iduna is a poly(ADP-ribose) (PAR)-dependent E3 ubiquitin ligase that regulates cellular responses such as proteasomal degradation and DNA repair upon interaction with its substrate. We identified a highly cationic region within the PAR-binding motif of Iduna; the region was similar among various species and showed amino acid sequence similarity with that of known cell-penetrating peptides (CPPs). We hypothesized that this Iduna-derived cationic sequence-rich peptide (Iduna) could penetrate the cell membrane and deliver macromolecules into cells...
March 8, 2018: International Journal of Molecular Sciences
Juan Song, Fei Yin, Xia Li, Na Dong, Yingjie Zhu, Yanan Shao, Baoli Chen, Wei Jiang, Chen-Zhong Li
We developed a novel approach to determine formamidopyrimidine DNA glycosylase (FPG) activity by taking advantage of target-induced self-primed rolling circle amplification (RCA) and magnetic nanoprobes. Herein, a unique nick (8-oxoguanine, 8-oxoG) was positioned in duplex DNA containing P-circle and P1 , which together serve as a FPG substrate, RCA template, and RCA primer probe. The presence of FPG specifically binds 8-oxoG and cleaves the P-circle into two parts, producing 5'-phosphoryl termini. A phosphodiester bond between the 5'-phosphoryl and 3'-hydroxyl termini was formed with the addition of T4 DNA ligase, producing an unnicked circular strand...
March 8, 2018: Analyst
Elliott Ferris, Lisa M Abegglen, Joshua D Schiffman, Christopher Gregg
The identity of most functional elements in the mammalian genome and the phenotypes they impact are unclear. Here, we perform a genome-wide comparative analysis of patterns of accelerated evolution in species with highly distinctive traits to discover candidate functional elements for clinically important phenotypes. We identify accelerated regions (ARs) in the elephant, hibernating bat, orca, dolphin, naked mole rat, and thirteen-lined ground squirrel lineages in mammalian conserved regions, uncovering ∼33,000 elements that bind hundreds of different regulatory proteins in humans and mice...
March 6, 2018: Cell Reports
Alisa Dewan, Mengtan Xing, Marie Benner Lundbæk, Raquel Gago-Fuentes, Carole Beck, Per Arne Aas, Nina-Beate Liabakk, Siri Sæterstad, Khac Thanh Phong Chau, Bodil Merete Kavli, Valentyn Oksenych
To ensure genome stability, mammalian cells employ several DNA repair pathways. Nonhomologous DNA end joining (NHEJ) is the DNA repair process that fixes double-strand breaks throughout the cell cycle. NHEJ is involved in the development of B and T lymphocytes through its function in V(D)J recombination and class switch recombination (CSR). NHEJ consists of several core and accessory factors, including Ku70, Ku80, XRCC4, DNA ligase 4, DNA-PKcs, Artemis, and XLF. Paralog of XRCC4 and XLF (PAXX) is the recently described accessory NHEJ factor that structurally resembles XRCC4 and XLF and interacts with Ku70/Ku80...
March 2018: FEBS Open Bio
Raquel Gago-Fuentes, Mengtan Xing, Siri Sæterstad, Antonio Sarno, Alisa Dewan, Carole Beck, Stefano Bradamante, Magnar Bjørås, Valentyn Oksenych
DNA repair consists of several cellular pathways which recognize and repair damaged DNA. The classical nonhomologous DNA end-joining (NHEJ) pathway repairs double-strand breaks in DNA. It is required for maturation of both B and T lymphocytes by supporting V(D)J recombination as well as B-cell differentiation during class switch recombination (CSR). Inactivation of NHEJ factors Ku70, Ku80, XRCC4, DNA ligase 4, DNA-PKcs, and Artemis impairs V(D)J recombination and blocks lymphocyte development. Paralogue of XRCC4 and XLF (PAXX) is an accessory NHEJ factor that has a significant impact on the repair of DNA lesions induced by ionizing radiation in human, murine, and chicken cells...
March 2018: FEBS Open Bio
Yunhee Cho, Hyeok Gu Kang, Seok-Jun Kim, Seul Lee, Sujin Jee, Sung Gwe Ahn, Min Jueng Kang, Joon Seon Song, Joon-Yong Chung, Eugene C Yi, Kyung-Hee Chun
Recurrence and drug resistance of breast cancer are still the main reasons for breast cancer-associated deaths. Cancer stem cell (CSC) model has been proposed as a hypothesis for the lethality of breast cancer. Molecular mechanisms underlying CSC maintenance are still unclear. In this study, we generated mammospheres derived from breast cancer MDA-MB231 cells and MCF7 cells to enrich CSCs and performed DNA microarray analysis. We found that the expression of carboxy terminus of HSP70-interacting protein (CHIP) E3 ubiquitin ligase was significantly downregulated in breast CSCs...
March 6, 2018: Cell Death and Differentiation
Haitao Luan, Bhopal Mohapatra, Timothy A Bielecki, Insha Mushtaq, Sameer Mirza, Tameka A Jennings, Robert J Clubb, Wei An, Dena Ahmed, Rokaya El Ansari, Matthew D Storck, Nitish K Mishra, Chittibabu Guda, Yuri M Sheinin, Jane L Meza, Srikumar Raja, Emad A Rakha, Vimla Band, Hamid Band
CHIP/STUB1 ubiquitin ligase is a negative co-chaperone for HSP90/HSC70, and its expression is reduced or lost in several cancers, including breast cancer. Using an extensive and well-annotated breast cancer tissue collection, we identified the loss of nuclear but not cytoplasmic CHIP to predict more aggressive tumorigenesis and shorter patient survival, with loss of CHIP in two-thirds of ErbB2+ and triple-negative breast cancers and in one-third of ER+ breast cancers. Reduced CHIP expression was seen in breast cancer patient-derived xenograft tumors and in ErbB2+ and triple-negative breast cancer cell lines...
March 6, 2018: Cancer Research
Agm Mostofa, Surendra R Punganuru, Hanumantha Rao Madala, Kalkunte S Srivenugopal
Whether the antimutagenic DNA repair protein MGMT works solo in human cells and if it has other cellular functions is not known. Here, we show that human MGMT associates with PCNA and in turn, with the cell cycle inhibitor, p21cip1 in glioblastoma and other cancer cell lines. MGMT protein was shown to harbor a nearly perfect PCNA-Interacting Protein (PIP box) motif. Isogenic p53-null H1299 cells were engineered to express the p21 protein by two different procedures. Reciprocal immunoprecipitation/western blotting, Far-western blotting, and confocal microscopy confirmed the specific association of MGMT with PCNA and the ability of p21 to strongly disrupt the MGMT-PCNA complexes in tumor cells...
March 2, 2018: Neoplasia: An International Journal for Oncology Research
Zhen Chen, Phillip A Lichtor, Adrian P Berliner, Jonathan C Chen, David R Liu
The evolution of sequence-defined synthetic polymers made of building blocks beyond those compatible with polymerase enzymes or the ribosome has the potential to generate new classes of receptors, catalysts and materials. Here we describe a ligase-mediated DNA-templated polymerization and in vitro selection system to evolve highly functionalized nucleic acid polymers (HFNAPs) made from 32 building blocks that contain eight chemically diverse side chains on a DNA backbone. Through iterated cycles of polymer translation, selection and reverse translation, we discovered HFNAPs that bind proprotein convertase subtilisin/kexin type 9 (PCSK9) and interleukin-6, two protein targets implicated in human diseases...
March 5, 2018: Nature Chemistry
Robert M Vaughan, Bradley M Dickson, Evan M Cornett, Joseph S Harrison, Brian Kuhlman, Scott B Rothbart
UHRF1 is a histone- and DNA-binding E3 ubiquitin ligase that functions with DNMT1 to maintain mammalian DNA methylation. UHRF1 facilitates DNMT1 recruitment to replicating chromatin through a coordinated mechanism involving histone and DNA recognition and histone ubiquitination. UHRF2 shares structural homology with UHRF1, but surprisingly lacks functional redundancy to facilitate DNA methylation maintenance. Molecular mechanisms uncoupling UHRF2 from DNA methylation maintenance are poorly defined. Through comprehensive and comparative biochemical analysis of recombinant human UHRF1 and UHRF2 reader and writer activities, we reveal conserved modes of histone PTM recognition but divergent DNA binding properties...
February 28, 2018: Nucleic Acids Research
Jason Liang, Bin-Zhong Li, Alexander P Tan, Richard D Kolodner, Christopher D Putnam, Huilin Zhou
Mms21, a subunit of the Smc5/6 complex, possesses an E3 ligase activity for the Small Ubiquitin-like MOdifier (SUMO). Here we show that the mms21-CH mutation, which inactivates Mms21 ligase activity, causes increased accumulation of gross chromosomal rearrangements (GCRs) selected in the dGCR assay. These dGCRs are formed by non-allelic homologous recombination between divergent DNA sequences mediated by Rad52-, Rrm3- and Pol32-dependent break-induced replication. Combining mms21-CH with sgs1Δ caused a synergistic increase in GCRs rates, indicating the distinct roles of Mms21 and Sgs1 in suppressing GCRs...
March 5, 2018: PLoS Genetics
Zhi Chen, Wei Zhang, Kaibiao Jiang, Bin Chen, Kun Wang, Lifeng Lao, Canglong Hou, Fei Wang, Caiguo Zhang, Hongxing Shen
Cullins, critical members of the cullin-RING ubiquitin ligases (CRLs), are often aberrantly expressed in different cancers. However, the underlying mechanisms regarding aberrant expression of these cullins and the specific substrates of CRLs in different cancers are mostly unknown. Here, we demonstrate that overexpressed CUL4B in human osteosarcoma cells forms an E3 complex with DNA damage binding protein 1 (DDB1) and DDB1- and CUL4-associated factor 13 (DCAF13). In vitro and in vivo analyses indicated that the CRL4BDCAF13 E3 ligase specifically recognized the tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) for degradation, and disruption of this E3 ligase resulted in PTEN accumulation...
March 2, 2018: Molecular Therapy. Nucleic Acids
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"