Ultraviolet Light-Induced and Spontaneous Recombination in Eukaryotes Roles of DNA Damage and DNA Repair Proteins

2003 ◽  
pp. 329-357
Author(s):  
Colin A. Bill ◽  
Jac A. Nickoloff
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Ultraviolet Light ◽  
Spontaneous Recombination ◽  
Dna Repair Proteins

scholarly journals Host DNA Repair Proteins in Response toPseudomonas aeruginosain Lung Epithelial Cells and in Mice

2010 ◽  
Vol 79 (1) ◽  
pp. 75-87 ◽  
Author(s):  
Min Wu ◽  
Huang Huang ◽  
Weidong Zhang ◽  
Shibichakravarthy Kannan ◽  
Andrew Weaver ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Epithelial Cells ◽  
Critical Role ◽  
Lung Epithelial Cells ◽  
Host Cells ◽  
Myeloperoxidase Activity ◽  
Gram Negative ◽  
Lung Epithelial ◽  
Dna Repair Proteins

ABSTRACTAlthough DNA repair proteins in bacteria are critical for pathogens' genome stability and for subverting the host defense, the role of host DNA repair proteins in response to bacterial infection is poorly defined. Here, we demonstrate, for the first time, that infection with the Gram-negative bacteriumPseudomonas aeruginosasignificantly altered the expression and enzymatic activity of 8-oxoguanine DNA glycosylase (OGG1) in lung epithelial cells. Downregulation of OGG1 by a small interfering RNA strategy resulted in severe DNA damage and cell death. In addition, acetylation of OGG1 is required for host responses to bacterial genotoxicity, as mutations of OGG1 acetylation sites increased Cockayne syndrome group B (CSB) protein expression. These results also indicate that CSB may be involved in DNA repair activity during infection. Furthermore, OGG1 knockout mice exhibited increased lung injury after infection withP. aeruginosa, as demonstrated by higher myeloperoxidase activity and lipid peroxidation. Together, our studies indicate thatP. aeruginosainfection induces significant DNA damage in host cells and that DNA repair proteins play a critical role in the host response toP. aeruginosainfection, serving as promising targets for the treatment of this condition and perhaps more broadly Gram-negative bacterial infections.

scholarly journals Acquired temozolomide resistance in MGMT-deficient glioblastoma cells is associated with regulation of DNA repair by DHC2

Brain ◽  
2019 ◽  
Vol 142 (8) ◽  
pp. 2352-2366 ◽  
Author(s):  
Guo-zhong Yi ◽  
Guanglong Huang ◽  
Manlan Guo ◽  
Xi’an Zhang ◽  
Hai Wang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Dna Methyltransferase ◽  
Molecular Mechanisms ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Dna Lesions ◽  
Dna Repair Proteins

Abstract The acquisition of temozolomide resistance is a major clinical challenge for glioblastoma treatment. Chemoresistance in glioblastoma is largely attributed to repair of temozolomide-induced DNA lesions by O6-methylguanine-DNA methyltransferase (MGMT). However, some MGMT-deficient glioblastomas are still resistant to temozolomide, and the underlying molecular mechanisms remain unclear. We found that DYNC2H1 (DHC2) was expressed more in MGMT-deficient recurrent glioblastoma specimens and its expression strongly correlated to poor progression-free survival in MGMT promotor methylated glioblastoma patients. Furthermore, silencing DHC2, both in vitro and in vivo, enhanced temozolomide-induced DNA damage and significantly improved the efficiency of temozolomide treatment in MGMT-deficient glioblastoma. Using a combination of subcellular proteomics and in vitro analyses, we showed that DHC2 was involved in nuclear localization of the DNA repair proteins, namely XPC and CBX5, and knockdown of either XPC or CBX5 resulted in increased temozolomide-induced DNA damage. In summary, we identified the nuclear transportation of DNA repair proteins by DHC2 as a critical regulator of acquired temozolomide resistance in MGMT-deficient glioblastoma. Our study offers novel insights for improving therapeutic management of MGMT-deficient glioblastoma.

scholarly journals H3K36me3 and PSIP1/LEDGF associate with several DNA repair proteins, suggesting their role in efficient DNA repair at actively transcribing loci

2021 ◽  
Vol 2 ◽  
pp. 83
Author(s):  
Jayakumar Sundarraj ◽  
Gillian C.A. Taylor ◽  
Alex von Kriegsheim ◽  
Madapura M Pradeepa
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Embryonic Stem ◽  
Adaptor Proteins ◽  
Transcriptional Elongation ◽  
Pwwp Domain ◽  
Stable Isotope Labelling ◽  
Homology Directed Repair ◽  
Dna Repair Proteins

Background: Trimethylation at histone H3 at lysine 36 (H3K36me3) is associated with expressed gene bodies and recruit proteins implicated in transcription, splicing and DNA repair. PC4 and SF2 interacting protein (PSIP1/LEDGF) is a transcriptional coactivator, possesses an H3K36me3 reader PWWP domain. Alternatively spliced isoforms of PSIP1 binds to H3K36me3 and suggested to function as adaptor proteins to recruit transcriptional modulators, splicing factors and proteins that promote homology-directed repair (HDR), to H3K36me3 chromatin. Methods: We performed chromatin immunoprecipitation of H3K36me3 followed by quantitative mass spectrometry (qMS) to identify proteins associated with H3K36 trimethylated chromatin in mouse embryonic stem cells (mESCs). We also performed stable isotope labelling with amino acids in cell culture (SILAC) followed by qMS for a longer isoform of PSIP1 (PSIP/p75) and MOF/KAT8 in mESCs and mouse embryonic fibroblasts ( MEFs). Furthermore, immunoprecipitation followed by western blotting was performed to validate the qMS data. DNA damage in PSIP1 knockout MEFs was assayed by a comet assay. Results: Proteomic analysis shows the association of proteins involved in transcriptional elongation, RNA processing and DNA repair with H3K36me3 chromatin. Furthermore, we show DNA repair proteins like PARP1, gamma H2A.X, XRCC1, DNA ligase 3, SPT16, Topoisomerases and BAZ1B are predominant interacting partners of PSIP /p75. We further validated the association of PSIP/p75 with PARP1, hnRNPU and gamma H2A.X  and also demonstrated accumulation of damaged DNA in PSIP1 knockout MEFs. Conclusions: In contrast to the previously demonstrated role of H3K36me3 and PSIP/p75 in promoting homology-directed repair (HDR), our data support a wider role of H3K36me3 and PSIP1 in maintaining the genome integrity by recruiting proteins involved in DNA damage response pathways to the actively transcribed loci.

scholarly journals Western Faculty Profile: Dr. Murray Junop

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Violet Liu
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Molecular Mechanism ◽  
Associate Professor ◽  
Primary Research ◽  
X Ray ◽  
X Ray Crystallography ◽  
Dna Repair Proteins ◽  
Editorial Review ◽  
Insight Into

Dr. Murray Junop is an Associate Professor and the Associate Undergraduate Chair in the Biochemistry Department at Western University. His primary research focuses on using x-ray crystallography to determine macromolecular structures crucial for the repair of various types of DNA damage. Ultimately, understanding the structures of these DNA repair proteins not only sheds insight into their function and molecular mechanism, but also provides necessary information for developing new anticancer therapies. Dr. Junop teaches undergraduate and graduate level courses offered in the department of Biochemistry. Violet Liu, a Reviewer on the Editorial Review Board at WURJ-HNS, had the pleasure of interviewing Dr. Junop to learn more about his career in research and his advice to students.

scholarly journals DNA repair by Rad52 liquid droplets

2019 ◽  
Author(s):  
Roxanne Oshidari ◽  
Richard Huang ◽  
Maryam Medghalchi ◽  
Elizabeth Y.W. Tse ◽  
Nasser Ashgriz ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Damage ◽  
Dna Repair ◽  
Phase Separation ◽  
Liquid Phase ◽  
Nuclear Periphery ◽  
Liquid Phase Separation ◽  
Liquid Droplets ◽  
Cellular Processes ◽  
Dna Repair Proteins

Cellular processes are influenced by liquid phase separation, but its role in DNA repair is unclear. Here, we show that in Saccharomyces cerevisiae, Rad52 DNA repair proteins at different DNA damage sites assemble liquid droplets that fuse into a repair centre droplet. This larger droplet concentrates tubulin and projects short aster-like microtubule filaments, which tether the droplet to longer microtubule filaments mediating the mobilization of damaged DNA to the nuclear periphery for repair.

scholarly journals Poly(ADP-ribosyl)ation temporally confines SUMO-dependent ataxin-3 recruitment to control DNA double-strand break repair

2021 ◽  
pp. jcs.247809
Author(s):  
Annika Pfeiffer ◽  
Laura K. Herzog ◽  
Martijn S. Luijsterburg ◽  
Rashmi G. Shah ◽  
Magdalena B. Rother ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Time Window ◽  
Strand Break ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Dna Double Strand Break ◽  
Dna Repair Proteins ◽  
Short Time Window ◽  
Short Time

DNA damage-induced SUMOylation serves as a signal for two antagonizing proteins that both stimulate repair of DNA double strand breaks (DSBs). Here, we demonstrate that the SUMO-dependent recruitment of the deubiquitylating enzyme ataxin-3 to DSBs, unlike recruitment of the ubiquitin ligase RNF4, additionally depends on PARP1-mediated poly(ADP-ribosyl)ation (PARylation). The co-dependence of ataxin-3 recruitment on PARylation and SUMOylation temporally confines its presence at DSBs to a short time window directly following detection of the DNA damage. We propose that this mechanism ensures that ataxin-3 prevents the premature removal of DNA repair proteins only during the early phase of the DSB response and does not interfere with the subsequent timely displacement of DNA repair proteins by RNF4. Thus, our data show that PARylation differentially regulates SUMO-dependent recruitment of ataxin-3 and RNF4 to DSBs, explaining how both proteins can play a stimulatory role at DSBs despite their opposing activities.

MAD2 Interacts with DNA Repair Proteins and Negatively Regulates DNA Damage Repair

2008 ◽  
Vol 381 (1) ◽  
pp. 24-34 ◽  
Author(s):  
Maggie K.L. Fung ◽  
Hui-Ying Han ◽  
Steve C.L. Leung ◽  
Hiu Wing Cheung ◽  
Annie L.M. Cheung ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Dna Damage Repair ◽  
Damage Repair ◽  
Dna Repair Proteins

scholarly journals Dimerization of MORC2 through its C-terminal coiled-coil domain enhances chromatin dynamics and promotes DNA repair

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Hong-Yan Xie ◽  
Tai-Mei Zhang ◽  
Shu-Yuan Hu ◽  
Zhi-Ming Shao ◽  
Da-Qiang Li
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Cell Survival ◽  
Zinc Finger Protein ◽  
Coiled Coil ◽  
Dna Interaction ◽  
Chromatin Dynamics ◽  
Histone H2ax ◽  
Finger Protein ◽  
Dna Repair Proteins

AbstractDecondesation of the highly compacted chromatin architecture is essential for efficient DNA repair, but how this is achieved remains largely unknown. Here, we report that microrchidia family CW-type zinc finger protein 2 (MORC2), a newly identified ATPase-dependent chromatin remodeling enzyme, is required for nucleosome destabilization after DNA damage through loosening the histone-DNA interaction. Depletion of MORC2 attenuates phosphorylated histone H2AX (γH2AX) focal formation, compromises the recruitment of DNA repair proteins, BRCA1, 53BP1, and Rad51, to sites of DNA damage, and consequently reduces cell survival following treatment with DNA-damaging chemotherapeutic drug camptothecin (CPT). Furthermore, we demonstrate that MORC2 can form a homodimer through its C-terminal coiled-coil (CC) domain, a process that is enhanced in response to CPT-induced DNA damage. Deletion of the C-terminal CC domain in MORC2 disrupts its homodimer formation and impairs its ability to destabilize histone-DNA interaction after DNA damage. Consistently, expression of dimerization-defective MORC2 mutant results in impaired the recruitment of DNA repair proteins to damaged chromatin and decreased cell survival after CPT treatment. Together, these findings uncover a new mechanism for MORC2 in modulating chromatin dynamics and DDR signaling through its c-terminal dimerization.

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