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MECHANISM AND REGULATION OF DNA RECOMBINATION IN SACCHAROMYCES CEREVISIAE

酿酒酵母DNA重组的机制和调控

基本信息

批准号：
10574599
负责人：
Grzegorz A Ira
金额：
$ 35.5万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-05-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10574599
关键词：
Affect Aging Antibodies Attenuated Award Cell Aging Cell Death Cell Nucleus Cells Chromosomal Breaks Chromosomes Chronic Complementary DNA DNA DNA Damage DNA Double Strand Break DNA Repair DNA Structure Data Disease Enzymes Event Foundations Frequencies Future Gene Silencing Generations Genes Genetic Recombination Genome Genome Stability Genomic Instability Goals Grant Heart failure Homeostasis Human Inflammation Inflammatory Response Innate Immune Response Iron Lead Ligation Malignant Neoplasms Maps Mediating Membrane Fusion Methodology Methods Mitochondria Mitochondrial DNA Monitor Nature Nerve Degeneration Nonhomologous DNA End Joining Nuclear Organism Parkinson Disease Pathway interactions Pattern Production Regulation Retrotransposition Retrotransposon Ribosomal DNA Role Saccharomyces cerevisiae Single-Stranded DNA Site Source System Testing Therapeutic Work Yeasts design ds-DNA endonuclease extrachromosomal DNA human disease infancy mitochondrial membrane mutant nuclease prevent protein misfolding repaired telomere tumor

项目摘要

Most of a cell’s DNA is packaged into chromosomes located within the nucleus. An additional small circular genome encoding only a few genes is located in the mitochondria. In some circumstances, cells release extrachromosomal pieces of DNA from mitochondrial DNA (mtDNA), from the nuclear genome or in the form of retrotransposon cDNA (rt-cDNA). There are two consequences of DNA fragment release. First, many organisms activate an innate immune response that may result in chronic inflammation and cell death. This inflammation may lead to severe diseases in human including some cases of heart failure, Parkinson’s disease or aging- related chronic inflammation. Second, released DNA can be inserted at DNA double strand breaks (DSBs) causing genome instability. Insertions of mtDNA, rt-cDNA and chromosome fragments destabilize the genome and are common in cancer, whereas rare gene insertions at the V(D)J locus constitute a pathway of antibody diversification. Despite a large body of evidence showing severe consequences of the release of DNA fragments, it remains unknown what cellular events lead to its generation. The goal of this proposal is to understand the mechanisms of free DNA formation and its insertion at DSBs. We will: (i) develop a high throughput method to capture and sequence free DNA, (ii) understand the mechanism of insertion of free DNA at DSBs by nonhomologous end joining and by alternative end joining, and (iii) decipher the mechanisms of linear DNA fragment release from mitochondria and from the nuclear genome.

细胞的大部分DNA被包装成位于细胞核内的染色体。一个额外的小圆