Mechanisms of DNA Recombination and Genome Rearrangements: Intersection Between Homologous Recombination, DNA Replication and DNA Repair

Erscheinungsjahr 2018
ISBN: 978-0-12-813979-0
Verlag: ACADEMIC PR INC

Buch, Englisch, Band 601, 434 Seiten, Format (B × H): 152 mm x 229 mm, Gewicht: 748 g

Reihe: Methods in Enzymology

Mechanisms of DNA Recombination and Genome Rearrangements: Intersection between Homologous Recombination, DNA Replication and DNA Repair, Volume 601, the latest release in the Methods in Enzymology series, continues the legacy of this premier serial with quality chapters authored by leaders in the field.

Homologous genetic recombination remains the most enigmatic process in DNA metabolism. The molecular machines of recombination preserve the integrity of the genetic material in all organisms and generate genetic diversity in evolution. The same molecular machines that support genetic integrity by orchestrating accurate repair of the most deleterious DNA lesions, however, also promote survival of cancerous cells and emergence of radiation and chemotherapy resistance. This two-volume set offers a comprehensive set of cutting edge methods to study various aspects of homologous recombination and cellular processes that utilize the enzymatic machinery of recombination. The chapters are written by the leading researches and cover a broad range of topics from the basic molecular mechanisms of recombinational proteins and enzymes to emerging cellular techniques and drug discovery efforts.

Zielgruppe

Biochemists, biophysicists, molecular biologists, analytical chemists, and physiologists

Autoren/Hrsg.

Spies, Maria

Malkova, Anna

Weitere Mitwirkende

Malkova, Anna

Fachgebiete

• Naturwissenschaften Biowissenschaften Enzymologie
• Naturwissenschaften Biowissenschaften Biochemie (nichtmedizinisch)
• Naturwissenschaften Biowissenschaften Biowissenschaften Genetik und Genomik (nichtmedizinisch)
• Naturwissenschaften Biowissenschaften Molekularbiologie
• Naturwissenschaften Biowissenschaften Biowissenschaften DNA und Transgene Organismen

Inhaltsverzeichnis

1. Using the Flp recombinase to induce site-specific nicks Lotte Bjergbaek 2. Synthesis from D-loops Wolf-Dietrich Heyer 3. Bacteriophage T4 system as a model for recombination/replication interface Scott Morrical 4. Inducing and detecting mitotic DNA synthesis at difficult-to-replicate loci Ian Hickson 5. Reporter system to study the RNA-DNA recombination Francesca Storici 6. Assaying recombination and mutagenesis at DNA nicks Nancy Maizels 7. Recovery of alternative end-joining repair products from Drosophila embryos Mitch McVey 8. High-throughput analysis of DNA break-induced chromosome rearrangements by amplicon sequencing Steven Roberts 9. Analysis of mutagenesis associated with recombination Jim Haber 10. Investigation of break-induced replication in yeast Anna Malkova 11. Dissecting the dual endo- and exonuclease activity of MRE11 (MRN) with small molecules John Tainer and Davide Moiani 12. RAD52 inhibition Ashley Spies 13. Structure-guided, fragment-based drug discovery against RAD51 recombinase: targeting a protein-peptide interface Thomas Blundell 14. Molecular intermediates of recombination in meiosis (methods, like 2D, and others) Neil Hunter 15. S1-seq method for mapping DSB resection endpoints Scott Keney 16. Methods for studying the roles of the Sgs1-Top3-Rmi1 helicase/decatenase complex in meiotic recombination intermediate metabolism Michael Lichten 17. Live cell imaging of heterochromatin repair in Drosophila cells Irene Chiolo 18. Analysis of meiotic double-strand break initiation in mammals Galina Petukhova and Dan Camerini-Otero

Über Autor(innen)

Malkova, Anna
Graduate of the St. Petersburg State University, Russia (1987 MS diploma with honors (equivalent of cum laude) in Genetics and 1993 Ph.D. in Genetics), Dr. Anna Malkova is an Associate Professor of Biology Department at the University of Iowa College of Liberal Arts and Sciences.

Malkova's research is focused on DNA repair mechanisms. She investigates the repair of double-strand DNA breaks (DSBs), the most lethal type of DNA lesions. Using a dependable and powerful model system in yeast, where a single DSB is initiated by a site-specific HO endonuclease, she successfully demonstrated that imprecise or faulty repair of DSBs leads to structural genomic variations including mutations, copy number variations (CNVs), and chromosomal rearrangements similar to those that cause genetic diseases and cancer in humans. She has a longstanding interest in break-induced replication (BIR), a DSB repair pathway that repairs so-called one-ended DNA breaks, similar to those produced at eroded telomeres and by collapsed replication forks. In her postdoctoral work with Dr. James Haber (Brandeis University), she was among the first who identified this mechanism in eukaryotes. Studies in Malkova's laboratory provided important insights into the mechanism of BIR, which was found to be fundamentally different from the mechanism of S-phase DNA replication. In particular, it was discovered that BIR is carried out by a migrating bubble rather than by a replication fork, and leads to conservative inheritance of newly synthesized DNA. This unusual molecular mechanism explained bursts of genetic instability that were observed in association with BIR, and that were similar to those associated with cancer and other diseases rooted in genetic instability.

Work in Malkova's lab is supported by the National Institutes of Health (NIH). Anna serves as a member to the Cancer Etiology study section of NIH/NCI.