scholarly journals Effect of Damage Type on Stimulation of Human Excision Nuclease by SWI/SNF Chromatin Remodeling Factor

2003 ◽  
Vol 23 (12) ◽  
pp. 4121-4125 ◽  
Author(s):  
Ryujiro Hara ◽  
Aziz Sancar
Keyword(s):  
Chromatin Remodeling ◽  
Dna Lesions ◽  
Pyrimidine Dimer ◽  
Cyclobutane Pyrimidine Dimer ◽  
Nucleosomal Dna ◽  
Different Types ◽  
Damage Type ◽  
Low Rate ◽  
Stimulation Of

ABSTRACT To investigate the repair of different types of DNA lesions in chromatin, we prepared mononucleosomes containing an acetylaminofluorene-guanine adduct (AAF-G), a (6-4) photoproduct, or a cyclobutane pyrimidine dimer (CPD) and measured the repair of these lesions by reconstituted 6-factor human excision nuclease. We find that incorporation into nucleosomes inhibits the repair of CPD more severely than repair of the AAF-G adduct and the (6-4) photoproduct. Equally important, we find that SWI/SNF stimulates the removal of AAF-G and (6-4) photoproduct but not of CPD from nucleosomal DNA. These results shed new light on the low rate of repair of CPDs in human cells in vivo.

scholarly journals PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1

2012 ◽  
Vol 199 (2) ◽  
pp. 235-249 ◽  
Author(s):  
Alex Pines ◽  
Mischa G. Vrouwe ◽  
Jurgen A. Marteijn ◽  
Dimitris Typas ◽  
Martijn S. Luijsterburg ◽  
...  
Keyword(s):  
Nucleotide Excision Repair ◽  
Chromatin Remodeling ◽  
Excision Repair ◽  
Dna Lesions ◽  
Subsequent Removal ◽  
Wd40 Repeat ◽  
Nucleotide Excision ◽  
Efficient Recognition

The WD40-repeat protein DDB2 is essential for efficient recognition and subsequent removal of ultraviolet (UV)-induced DNA lesions by nucleotide excision repair (NER). However, how DDB2 promotes NER in chromatin is poorly understood. Here, we identify poly(ADP-ribose) polymerase 1 (PARP1) as a novel DDB2-associated factor. We demonstrate that DDB2 facilitated poly(ADP-ribosyl)ation of UV-damaged chromatin through the activity of PARP1, resulting in the recruitment of the chromatin-remodeling enzyme ALC1. Depletion of ALC1 rendered cells sensitive to UV and impaired repair of UV-induced DNA lesions. Additionally, DDB2 itself was targeted by poly(ADP-ribosyl)ation, resulting in increased protein stability and a prolonged chromatin retention time. Our in vitro and in vivo data support a model in which poly(ADP-ribosyl)ation of DDB2 suppresses DDB2 ubiquitylation and outline a molecular mechanism for PARP1-mediated regulation of NER through DDB2 stabilization and recruitment of the chromatin remodeler ALC1.

scholarly journals Nucleosome breathing and remodeling constrain CRISPR-Cas9 function

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
R Stefan Isaac ◽  
Fuguo Jiang ◽  
Jennifer A Doudna ◽  
Wendell A Lim ◽  
Geeta J Narlikar ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Dna Sequences ◽  
Surveillance System ◽  
Dynamic Properties ◽  
Eukaryotic Cells ◽  
Chromatin Remodelers ◽  
Nucleosomal Dna ◽  
Eukaryotic Chromatin ◽  
Versatile Tool

The CRISPR-Cas9 bacterial surveillance system has become a versatile tool for genome editing and gene regulation in eukaryotic cells, yet how CRISPR-Cas9 contends with the barriers presented by eukaryotic chromatin is poorly understood. Here we investigate how the smallest unit of chromatin, a nucleosome, constrains the activity of the CRISPR-Cas9 system. We find that nucleosomes assembled on native DNA sequences are permissive to Cas9 action. However, the accessibility of nucleosomal DNA to Cas9 is variable over several orders of magnitude depending on dynamic properties of the DNA sequence and the distance of the PAM site from the nucleosome dyad. We further find that chromatin remodeling enzymes stimulate Cas9 activity on nucleosomal templates. Our findings imply that the spontaneous breathing of nucleosomal DNA together with the action of chromatin remodelers allow Cas9 to effectively act on chromatin in vivo.

scholarly journals Fungal cryptochrome with DNA repair activity reveals an early stage in cryptochrome evolution

2015 ◽  
Vol 112 (49) ◽  
pp. 15130-15135 ◽  
Author(s):  
Victor G. Tagua ◽  
Marcell Pausch ◽  
Maike Eckel ◽  
Gabriel Gutiérrez ◽  
Alejandro Miralles-Durán ◽  
...  
Keyword(s):  
Dna Repair ◽  
Blue Light ◽  
Early Stage ◽  
Single Gene ◽  
Dna Lesions ◽  
Pyrimidine Dimer ◽  
Dependent Manner ◽  
Phycomyces Blakesleeanus

DASH (Drosophila, Arabidopsis, Synechocystis, Human)-type cryptochromes (cry-DASH) belong to a family of flavoproteins acting as repair enzymes for UV-B–induced DNA lesions (photolyases) or as UV-A/blue light photoreceptors (cryptochromes). They are present in plants, bacteria, various vertebrates, and fungi and were originally considered as sensory photoreceptors because of their incapability to repair cyclobutane pyrimidine dimer (CPD) lesions in duplex DNA. However, cry-DASH can repair CPDs in single-stranded DNA, but their role in DNA repair in vivo remains to be clarified. The genome of the fungus Phycomyces blakesleeanus contains a single gene for a protein of the cryptochrome/photolyase family (CPF) encoding a cry-DASH, cryA, despite its ability to photoreactivate. Here, we show that cryA expression is induced by blue light in a Mad complex-dependent manner. Moreover, we demonstrate that CryA is capable of binding flavin (FAD) and methenyltetrahydrofolate (MTHF), fully complements the Escherichia coli photolyase mutant and repairs in vitro CPD lesions in single-stranded and double-stranded DNA with the same efficiency. These results support a role for Phycomyces cry-DASH as a photolyase and suggest a similar role for cry-DASH in mucoromycotina fungi.

scholarly journals Pioneer transcription factors in chromatin remodeling: the kinetic proofreading view

2020 ◽  
Author(s):  
Helmut Schiessel ◽  
Ralf Blossey
Keyword(s):  
Transcription Factors ◽  
Chromatin Remodeling ◽  
Chromatin Structure ◽  
Gene Activation ◽  
Transcriptional Initiation ◽  
Nucleosomal Dna ◽  
Different Types ◽  
Kinetic Proofreading ◽  
Fine Tune

Pioneer transcription factors are a recently defined class of transcription factors which can bind directly to nucleosomal DNA; they play a key role in gene activation in certain pathways. Here we quantify their role in the initiation of nucleosome displacement within the kinetic proofreading scenario of chromatin remodeling. The model allows to perform remodeling efficiency comparisons for scenarios involving different types of transcription factors and remodelers as a function of their binding and unbinding rates and concentrations. Our results demonstrate a novel way to fine-tune the specificity of processes that modify the chromatin structure in transcriptional initiation.

scholarly journals Genome-wide transcription-coupled repair inEscherichia coliis mediated by the Mfd translocase

2017 ◽  
Vol 114 (11) ◽  
pp. E2116-E2125 ◽  
Author(s):  
Ogun Adebali ◽  
Yi-Ying Chiou ◽  
Jinchuan Hu ◽  
Aziz Sancar ◽  
Christopher P. Selby
Keyword(s):  
High Throughput Sequencing ◽  
Excision Repair ◽  
Coupling Factor ◽  
Pyrimidine Dimer ◽  
Cyclobutane Pyrimidine Dimer ◽  
Predominant Role ◽  
Genome Wide Analysis ◽  
Genome Wide

We used high-throughput sequencing of short, cyclobutane pyrimidine dimer-containing ssDNA oligos generated during repair of UV-induced damage to study that process at both mechanistic and systemic levels inEscherichia coli. Numerous important insights on DNA repair were obtained, bringing clarity to the respective roles of UvrD helicase and Mfd translocase in repair of UV-induced damage. Mechanistically, experiments showed that the predominant role of UvrD in vivo is to unwind the excised 13-mer from dsDNA and that mutation ofuvrDresults in remarkable protection of that oligo from exonuclease activity as it remains hybridized to the dsDNA. Genome-wide analysis of the transcribed strand/nontranscribed strand (TS/NTS) repair ratio demonstrated that deletion ofmfdglobally shifts the distribution of TS/NTS ratios downward by a factor of about 2 on average for the most highly transcribed genes. Even for the least transcribed genes, Mfd played a role in preferential repair of the transcribed strand. On the other hand, mutation ofuvrD, if anything, slightly pushed the distribution of TS/NTS ratios to higher ratios. These results indicate that Mfd is the transcription repair-coupling factor whereas UvrD plays a role in excision repair by aiding the catalytic turnover of excision repair proteins.

scholarly journals The RSC complex remodels nucleosomes in transcribed coding sequences and promotes transcription in Saccharomyces cerevisiae

2020 ◽  
Author(s):  
Emily Biernat ◽  
Jeena Kinney ◽  
Kyle Dunlap ◽  
Christian Rizza ◽  
Chhabi K Govind
Keyword(s):  
Rna Polymerase Ii ◽  
Chromatin Remodeling ◽  
Biological Processes ◽  
Strongly Correlated ◽  
Rna Pol Ii ◽  
Coding Sequences ◽  
Pol Ii ◽  
Chromatin Remodeling Complex ◽  
Nucleosomal Dna

RSC (Remodels the Structure of Chromatin) is a conserved ATP-dependent chromatin remodeling complex that regulates many biological processes, including transcription by RNA polymerase II (Pol II). We report that not only RSC binds to nucleosomes in coding sequences (CDSs) but also remodels them to promote transcription. RSC MNase ChIP-seq data revealed that RSC-protected fragments were very heterogenous (~80 bp to 180 bp) compared to the sharper profile displayed by the MNase inputs (140 bp to 160 bp), supporting the idea that RSC activity promotes accessibility of nucleosomal DNA. Importantly, RSC binding to +1 nucleosomes and CDSs, but not with -1 nucleosomes, strongly correlated with Pol II occupancies suggesting that the RSC enrichment in CDSs is important for efficient transcription. This is further supported by a similar heterogenous distribution of Pol II-protected fragments. As such, the genes harboring high-levels of RSC in their CDSs were the most strongly affected by ablating RSC function. Altogether, this study provides a mechanism by which RSC-mediated remodeling aids in RNA Pol II traversal though coding sequence nucleosomes in vivo.

Potential Uses of Vinegar as a Medicine and Related in vivo Mechanisms

2016 ◽  
Vol 86 (3-4) ◽  
pp. 127-151 ◽  
Author(s):  
Zeshan Ali ◽  
Zhenbin Wang ◽  
Rai Muhammad Amir ◽  
Shoaib Younas ◽  
Asif Wali ◽  
...  
Keyword(s):  
Chemical Structure ◽  
Review Paper ◽  
Heart Diseases ◽  
Folk Medicine ◽  
Active Role ◽  
Current Review ◽  
Different Types ◽  
Positive Effect

While the use of vinegar to fi ght against infections and other crucial conditions dates back to Hippocrates, recent research has found that vinegar consumption has a positive effect on biomarkers for diabetes, cancer, and heart diseases. Different types of vinegar have been used in the world during different time periods. Vinegar is produced by a fermentation process. Foods with a high content of carbohydrates are a good source of vinegar. Review of the results of different studies performed on vinegar components reveals that the daily use of these components has a healthy impact on the physiological and chemical structure of the human body. During the era of Hippocrates, people used vinegar as a medicine to treat wounds, which means that vinegar is one of the ancient foods used as folk medicine. The purpose of the current review paper is to provide a detailed summary of the outcome of previous studies emphasizing the role of vinegar in treatment of different diseases both in acute and chronic conditions, its in vivo mechanism and the active role of different bacteria.

Stimulation of ovarian progesterone secretion by oxytocin in vivo

1988 ◽  
Vol 117 (4_Suppl) ◽  
pp. S199-S200
Author(s):  
E. DIETRICH ◽  
K. RENTELMANN ◽  
W. WUTTKE
Keyword(s):  
Progesterone Secretion ◽  
Stimulation Of
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