Ation mechanism, FAK signaling One of the best characterized examples of the modulation of chromatin structure in response to DNA-Sch Is the ATM / ATR / DNA-PK phosphorylation of histone H2AX variant chromatin flanking DSB sites. This serves as a signal for the recruitment of factors lead to DNA-Sch The answer and chromatin modification of other components which are assembled in order to repair the DSB f rdern And verst The DSB signal strengths. Factors associated with H2AX, both the integration and dissociation of H2AX histone H2A and exchange with Herk Mmlichen f rdern. These factors closing S FACT, DNA-PK and PARP-1. It could be shown that indeed involved in the exchange process H2AX, by phosphorylation is stimulated and inhibited by ADP-ribosylation.
Recently it was shown that the chromatin remodeling enzyme ALC1 quickly recruited to DNA-Sch Its sites via an interaction with a poly OURTH PARP, activation of its ATPase and chromatin remodeling activity KRN 633 Catalyze nucleosome sliding and stimulates th PARP. Also, thanks to its R In PARP-1 chromatin remodeling play an R In the regulation of transcription. The deregulated expression of genes through mechanisms known to occur in both genetic and epigenetic tumorigenesis and tumor progression to pr Sentieren. Biochemical and in vivo that either PARP tr Gt for compaction or decondensation of chromatin function under physiological conditions. For F Ll, it was suggested that PARP-1 is a repressive chromatin structure at sites of transient DNA-Sch The set to block transcription and DNA repair easier.
Furthermore, a PARP localized in the promoters of most actively transcribed genes, suggesting that it plays a role The F Promotion of the formation of chromatin structures, the permissive, are to the transcript. However, a PARP regulates only a subset of genes to which they bind, and it has positive and negative transcription. Thus, the gene regulation by PARP-1 is a complex process that may involve several mechanisms and additionally be modulated Posts USEFUL GE. W While the remains of the r 2 of the PARP in the regulation of transcription largely subject to debate Rt. Recent studies have begun to polyation a dependent Ngig PARP to associate with the DNA methylation, a stable epigenetic marks are transmitted to daughter cells during cell division and repression of gene expression is associated.
The chromatin insulator CTCF plays a role The main effects of PARP on DNA methylation. CTCF is an activator of PARP Automodifikationsdom Ne one, which in turn inhibits DNA methyltransferase activity t Dnmt1 that affect the methylation status of genomic DNA and CpG island regions. Recently, Krishnakumar and Kraus been shown that a PARP regulates chromatin structure and transcription dependent by histone demethylase KDM5B Dependent. Other mechanisms link 2 PARP 1 and PARP in genome surveillance and cancer, M Deficiencies in other biological processes such as PARP-1, 2 and PARP cancer 335,1:328 346 chromosome segregation and loss of telomeres k Nnte to genomic instability, a characteristic of most cancers result.
PARP-1, 2 and PARP chromosome segregation, segregation of homologous chromosomes may need during the metaphase anaphase transition is a dramatic event that will cause the inheritance of a complete set of chromosomes in each cell erf daughter Stirred cell division. Essentially duplicated chromosomes are condensed and the metaphase plate, where chromatid sisters then aligned separately by microtubules to kinetochores. This process requires time and get the r Spatial coordination of a variety of proteins, genomic stability T over successive rounds of cell division remains. Tats Chlich chromosomal and centrosome amplification maldistribution Rkung h occur Frequently in cancer cells. PARP 1 and 2 with functional centromeres PARP S Mammal, a cell cycle-dependent assigned Ngigen manner and interacts with the parent