Double Strand Break Repair Within Constitutive Heterochromatin


Book Description

Heterochromatin is the tightly packed form of repetitive DNA, essential for cell viability. Its highly compacted and repetitive nature renders DSB repair a challenging process that cells need to overcome in order to maintain their genome integrity. Developing a highly specific and robust CRISPR/Cas9 system to target pericentric heterochromatin, we showed that DSBs in G1 are positionally stable and repaired by NHEJ. In S/G2, they relocate to the periphery of this domain to be repaired by HR. This relocation process is dependent of resection and RAD51 exclusion from the core domain of heterochromatin. If these breaks fail to relocate, they are repaired within heterochromatin by NHEJ or SSA. On the other hand, DSBs in centromeric heterochromatin activate both NHEJ and HR throughout the cell cycle. Our results reveal the differential repair pathway choice between centromeric and pericentric heterochromatin that also regulates the DSB position.




Silencing, Heterochromatin and DNA Double Strand Break Repair


Book Description

The field of DNA repair is vast and advancing rapidly. Recent investigations have begun to focus on the involvement of chromatin in the repair of broken DNA. Although I have no doubt that many breakthroughs in our understanding of chromatin, chromatin regulation, and DNA repair lie in our future, presently this is a new line in inquiry. As such there are many, many unanswered questions. Indeed, most of the correct questions have probably not even been asked yet. Here I have attempted to present a review of some of the current body of knowledge that may prove relevant to understanding the role of chromatin in DNA repair. Because the volume of research, and the relevant findings, come from a staggering array of labs, systems, and ideas I have focused primarily on findings developed from the study of the budding yeast Saccharomyces cerevisiae. Unfortunately, this means that I have left out a great deal of information. It is my hope, however, that the information I do detail, particularly in Chapter 1, will give a flavor for the scope of the problem and perhaps highlight some of the interesting directions this field is taking, or may one day take. I would also point out that the primary research that is presented herein is not in any way meant to represent the comprehensive scope of research being performed. To understand DNA repair will require investigation from innumerable labs, performed by innumerable researchers, moving in unexpected directions.







The Role of the Chromatin Organization in DNA Double Strand Break Repair in Mouse Embryonic Stem Cells


Book Description

Multiple parameters can influence DNA repair, including local chromatin organization around the damage site, cell differentiation status, and a cell cycle state. Developing a CRISPR/Cas9 system in mouse embryonic stem cells for specific targeting chromatin types of interest, and HR-TIDE, a method to detect repair outcome, we were able to show that homologuos recombination frequency, despite often being low, is higher in embryonic stem cells than in differentiated cells. However, we could see that it is at least partially caused by cell cycle differences. We could also confirm that transcriptionally active chromatin is rather promoting homologous recombination, whereas facultative heterochromatin and bivalent domains represent a repressive environment. All in all, our data shed light on the role of bivalent chromatin and facultative heterochromatin in the process of DNA repair pathway choice.




DNA Recombination and Repair


Book Description

The processes of DNA recombination and repair are vital to cell integrity - an error can lead to disease such as cancer. It is therefore a large and exciting area of research and is also taught on postgraduate and undergraduate courses. This book is not a comprehensive view of the field, but a selection of the issues currently at the forefront of knowledge.




Chromatin and Disease


Book Description

This book includes a collection of articles with the broad theme of disease connection to chromatin structure and function. It elaborates on the molecular pharmacology of the drugs targeting chromatin structure and its components. The book contains up-to-date information about the chromatin structure and chromatin related diseases and drug functions. This work is the first endeavor to present different aspects encompassing the above theme.




Epigenetic Gene Expression and Regulation


Book Description

Epigenetic Gene Expression and Regulation reviews current knowledge on the heritable molecular mechanisms that regulate gene expression, contribute to disease susceptibility, and point to potential treatment in future therapies. The book shows how these heritable mechanisms allow individual cells to establish stable and unique patterns of gene expression that can be passed through cell divisions without DNA mutations, thereby establishing how different heritable patterns of gene regulation control cell differentiation and organogenesis, resulting in a distinct human organism with a variety of differing cellular functions and tissues. The work begins with basic biology, encompasses methods, cellular and tissue organization, topical issues in epigenetic evolution and environmental epigenesis, and lastly clinical disease discovery and treatment. Each highly illustrated chapter is organized to briefly summarize current research, provide appropriate pedagogical guidance, pertinent methods, relevant model organisms, and clinical examples. - Reviews current knowledge on the heritable molecular mechanisms that regulate gene expression, contribute to disease susceptibility, and point to potential treatment in future therapies - Helps readers understand how epigenetic marks are targeted, and to what extent transgenerational epigenetic changes are instilled and possibly passed onto offspring - Chapters are replete with clinical examples to empower the basic biology with translational significance - Offers more than 100 illustrations to distill key concepts and decipher complex science




Protein Phosphorylation in Human Health


Book Description

15 chapters on protein phosphorylation and human health written by expert scientists. Covers most important research hot points, such as Akt, AMPK and mTOR. Bridges the basic protein phosphorylation pathways with human health and diseases. Detailed and comprehensive text with excellent figure illustration.




Handbook of Epigenetics


Book Description

Handbook of Epigenetics: The New Molecular and Medical Genetics, Second Edition, provides a comprehensive analysis of epigenetics, from basic biology, to clinical application. Epigenetics is considered by many to be the new genetics in that many biological phenomena are controlled, not through gene mutations, but rather through reversible and heritable epigenetic processes. These epigenetic processes range from DNA methylation to prions. The biological processes impacted by epigenetics are vast and encompass effects in lower organisms and humans that include tissue and organ regeneration, X-chromosome inactivation, stem cell differentiation, genomic imprinting, and aging. The first edition of this important work received excellent reviews; the second edition continues its comprehensive coverage adding more current research and new topics based on customer and reader reviews, including new discoveries, approved therapeutics, and clinical trials. From molecular mechanisms and epigenetic technology, to discoveries in human disease and clinical epigenetics, the nature and applications of the science is presented for those with interests ranging from the fundamental basis of epigenetics, to therapeutic interventions for epigenetic-based disorders. - Timely and comprehensive collection of fully up-to-date reviews on epigenetics that are organized into one volume and written by leading figures in the field - Covers the latest advances in many different areas of epigenetics, ranging from basic aspects, to technologies, to clinical medicine - Written at a verbal and technical level that can be understood by scientists and college students - Updated to include new epigenetic discoveries, newly approved therapeutics, and clinical trials




Compendium of Histology


Book Description

This book has been designed to help medical students succeed with their histology classes, while using less time on studying the curriculum. The book can both be used on its own or as a supplement to the classical full-curriculum textbooks normally used by the students for their histology classes. Covering the same curriculum as the classical textbooks, from basic tissue histology to the histology of specific organs, this book is formatted and organized in a much simpler and intuitive way. Almost all text is formatted in bullets or put into structured tables. This makes it quick and easy to digest, helping the student get a good overview of the curriculum. It is easy to locate specific information in the text, such as the size of cellular structures etc. Additionally, each chapter includes simplified illustrations of various histological features. The aim of the book is to be used to quickly brush up on the curriculum, e.g. before a class or an exam. Additionally, the book includes guides to distinguish between the different histological tissues and organs that can be presented to students microscopically, e.g. during a histology spot test. This guide lists the specific characteristics of the different histological specimens and also describes how to distinguish a specimen from other similar specimens. For each histological specimen, a simplified drawing and a photomicrograph of the specimen, is presented to help the student recognize the important characteristics in the microscope. Lastly, the book contains multiple “memo boxes” in which parts of the curriculum are presented as easy-to-remember mnemonics.