Silencing Heterochromatin And Dna Double Strand Break Repair
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Silencing Heterochromatin And Dna Double Strand Break Repair
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Author : Kevin D. Mills
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-12-06
Silencing Heterochromatin And Dna Double Strand Break Repair written by Kevin D. Mills and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-06 with Science categories.
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.
Silencing Heterochromatin And Dna Double Strand Break Repair In Saccharomyces Cerevisiae
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Author : Kevin David Mills
language : en
Publisher:
Release Date : 1999
Silencing Heterochromatin And Dna Double Strand Break Repair In Saccharomyces Cerevisiae written by Kevin David Mills and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1999 with categories.
Repair Of Dna Double Strand Breaks In G1 Phase Cells
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Author : Anthony Thomas Tubbs
language : en
Publisher:
Release Date : 2014
Repair Of Dna Double Strand Breaks In G1 Phase Cells written by Anthony Thomas Tubbs and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014 with Electronic dissertations categories.
The two main DNA double-strand break (DSB) repair pathways are non-homologous end joining (NHEJ) and homologous recombination (HR). DNA ends are normally resected to form single-stranded overhangs to initiate HR, but resection severely limits repair by NHEJ. In G1-phase cells, NHEJ is the primary DNA DSB repair pathway, so DNA end resection must be restricted in these cells to prevent aberrant repair. Antigen receptor gene assembly occurs in G1-phase lymphocytes, using DNA DSB intermediates to generate a variable exon required for antigen binding. We show that the histone H2A variant, H2AX, which is phosphorylated by ATM kinase to generate gamma-H2AX in chromatin flanking DSBs, prevents the earliest steps of resection at RAG DSBs and other genotoxic DSBs in G1-phase lymphocytes. This gamma-H2AX function relies on its downstream factors MDC1 and RNF8 to concentrate 53BP1 at chromatin flanking the DSB, preventing the activity of resection machinery that can act in G1-phase cells. Resection in G1 is dependent on the protein CtIP, which has been previously shown to promote resection in S-G2 phases of the cell cycle. KAP-1 is a multifunctional adaptor protein that is involved in transcriptional silencing and maintenance of heterochromatin recently been implicated in repair of heterochromatic DNA DSBs. Here, we show that KAP-1 has a role in repair outside of heterochromatin, as it also promotes resection at RAG DSBs, along with CtIP. We have unexpectedly discovered that human KAP-1 blocks resection in mouse G1-phase lymphocytes in a dominant manner. The basis for this difference between human and mouse KAP-1 is a single amino acid polymorphism specific to primates located in a disordered region of the protein. Thus, we have established KAP-1 as part of the resection machinery in G1-phase cells that must be restricted by gamma-H2AX and 53BP1 to prevent resection and aberrant repair of DNA DSBs.
The Role Of Atm Signalling And Its Mediator Proteins In Dna Double Strand Break Repair
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Author : Andreas David William Kakarougkas
language : en
Publisher:
Release Date : 2012
The Role Of Atm Signalling And Its Mediator Proteins In Dna Double Strand Break Repair written by Andreas David William Kakarougkas and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012 with categories.
Although most DNA double strand breaks (DSBs) are repaired by DNA nonhomologous end!joining (NHEJ), DSBs at heterochromatin (HC) regions undergo repair by homologous recombination (HR) in G2 phase. Repair of DSBs at HC regions requires ATM-dependent KAP1 phosphorylation and subsequent HC relaxation. The mediator proteins facilitate DSB repair at HC in G1 phase by retaining ATM and hence pKAP1 at DSBs until the completion of repair. In this thesis, I investigated the role of the mediator proteins in enabling DSB repair in G2 phase. I demonstrate that the mediator proteins are required for the slow component of DSB repair in G2, which represents HR. They also promote ATM-dependent pKAP1 formation in G2 as in G1. In addition, I have described a role for MDC1 in Rad51 loading and for RNF8 in DNA resection. Moreover, I demonstrate that BRCA1 overcomes an inhibitory barrier by 53BP1 to resection by promoting a G2-specific enlargement in 53BP1 foci during HR that involves 53BP1 repositioning to the foci periphery and vacation from the central core. RPA foci form in the core devoid of 53BP1. 53BP1 has opposing roles in HR; it creates a restrictive barrier to resection but promotes pKAP1 and HC relaxation. RAP80 also inhibits resection by binding to ubiquitylated histones at DSBs. I demonstrate that the DUB enzyme, POH1, is required to overcome the barrier posed to resection by RAP80 since its depletion leads to deficient 53BP1 vacation of the central core and deficient resection. BRCA1 and POH1 cooperate during G2 phase to promote resection and DSB repair by HR. Additionally; I investigated the role(s) of the chromatin remodelers BAF180 and CHD7 in transcriptional silencing following DSB induction, a process that requires ATM, RNF8 and RNF168. I demonstrate that deficient transcriptional silencing leads to a DSB repair defect at early times post IR.
Protein Phosphorylation In Human Health
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Author : Cai Huang
language : en
Publisher: BoD – Books on Demand
Release Date : 2012-09-06
Protein Phosphorylation In Human Health written by Cai Huang and has been published by BoD – Books on Demand this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-09-06 with Medical categories.
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.
Fundamentals Of Chromatin
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Author : Jerry L. Workman
language : en
Publisher: Springer Science & Business Media
Release Date : 2013-12-04
Fundamentals Of Chromatin written by Jerry L. Workman and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-12-04 with Medical categories.
While there has been an increasing number of books on various aspects of epigenetics, there has been a gap over the years in books that provide a comprehensive understanding of the fundamentals of chromatin. Chromatin is the combination of DNA and proteins that make up the genetic material of chromosomes. Its primary function is to package DNA to fit into the cell, to strengthen the DNA to prevent damage, to allow mitosis and meiosis, and to control the expression of genes and DNA replication. The audience for this book is mainly newly established scientists and graduate students. Rather than going into the more specific areas of recent research on chromatin the chapters in this book give a strong, updated groundwork about the topic. Some the fundamentals that this book will cover include the structure of chromatin and biochemistry and the enzyme complexes that manage it.
Protecting The Code Dna Double Strand Break Repair Pathway Choice
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Author : David Maranon
language : en
Publisher: Frontiers Media SA
Release Date : 2023-03-31
Protecting The Code Dna Double Strand Break Repair Pathway Choice written by David Maranon and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2023-03-31 with Science categories.
Gene Regulation Epigenetics And Hormone Signaling
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Author : Subhrangsu S. Mandal
language : en
Publisher: John Wiley & Sons
Release Date : 2017-10-23
Gene Regulation Epigenetics And Hormone Signaling written by Subhrangsu S. Mandal and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-10-23 with Science categories.
The first of its kind, this reference gives a comprehensive but concise introduction to epigenetics before covering the many interactions between hormone regulation and epigenetics at all levels. The contents are very well structured with no overlaps between chapters, and each one features supplementary material for use in presentations. Throughout, major emphasis is placed on pathological conditions, aiming at the many physiologists and developmental biologists who are familiar with the importance and mechanisms of hormone regulation but have a limited background in epigenetics.
Regulation Of Dna Double Strand Break Repair By Local Chromatin Architecture
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Author : Sérgio Fernandes de Almeida
language : en
Publisher: Frontiers Media SA
Release Date : 2020-09-02
Regulation Of Dna Double Strand Break Repair By Local Chromatin Architecture written by Sérgio Fernandes de Almeida and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-09-02 with Science categories.
This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.
Chromosome Translocation
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Author : Yu Zhang
language : en
Publisher: Springer
Release Date : 2018-06-28
Chromosome Translocation written by Yu Zhang and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-06-28 with Medical categories.
This volume discusses various aspects of mechanisms and methodologies of chromosome translocations, ranging from a historical and clinical overview of chromosome translocations to the rapid development of the next-generation sequencing technologies, which has dramatically increased our understanding of the spectrum of chromosome translocations in human diseases. The book also introduces the mechanistic studies on chromosome deletions and their implications in cancer, and discusses the mechanisms of regulating chromothripsis, a unique complex type of chromosome translocation. It is a valuable resource for students and researchers alike, providing insights into chromosome translocations and, potentially, other genomic aberrations involved in understanding and curing human diseases.
