Responses to Telomere Loss

对端粒丢失的反应

• 批准号: 9106534
• 负责人: KENT G GOLIC
• 金额: $ 31.85万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9106534
• 关键词: Apoptosis; Caspase; Cell Death; Cells; Chromosomal Breaks; Chromosomal Stability; Chromosomes; DNA Damage; Development; Drosophila genus; Drosophila melanogaster; Ensure; Eukaryota; Failure; Female; Generations; Genes; Genetic; Genome; Germ Cells; Goals; Healed; Lead; Malignant Neoplasms; Organism; Parents; Pathway interactions; Play; Process; Property; Proteins; Quality Control; Resort; Role; Signal Transduction; TP53 gene; Telomere Maintenance; Testing; Work; Yeasts; cancer cell; coping; developmental disease; genome integrity; healing; interest; male; mutant; offspring; prevent; public health relevance; repaired; research study; response; sensor; telomere; telomere loss; transmission process

 DESCRIPTION (provided by applicant): The long-term objective of this work is to understand the mechanisms that organisms use to ensure that genome integrity is maintained from generation to generation and from cell to cell. Genomes are subject to damage in a variety of forms and have evolved a variety of mechanisms to repair damage, or to cope with failure. To maintain chromosome stability, the linear chromosomes of eukaryotes must be capped with telomeres. Loss of a single telomere is a particularly challenging form of genome damage, and most often results in apoptosis, rather than successful repair. Two forms of repair are known for this type of damage: healing, which refers to the addition of a new telomere on the non-telomeric end of a chromosome; or Break-Induced Replication (BIR), in which the broken chromosome copies information from another chromosome to replace the end that it is missing. Both types of repair are associated with alterations in the genome. Since this is generally undesirable, these modes of repair may be considered "repair of last resort". The work proposed here will investigate the germline responses to telomere loss. The goals are to identify the genetic controls that are used to detect and eliminate cells with this form of damage. Differences in the responses between male and female germlines will be explored. The experiments proposed here will also investigate the BIR mode of repair, which has not been previously demonstrated in any germline. This type of repair has additional interest because of its similarity to a form of telomere maintenance found in some cancer cells.

 描述（由应用程序提供）：这项工作的长期目标是了解生物体用来确保基因组完整性的机制，从而产生并从细胞到细胞。基因组受到各种形式的损害，并进化了多种修复损害或应对失败的机制。为了维持染色体稳定性，真核生物的线性染色体必须用端粒限制。损失两种形式的修复形式是这种损害：愈合，这是指在染色体的非高层末端添加新的端粒；或破裂引起的复制（BIR），其中损坏的染色体从另一个染色体复制信息以取代其缺失的末端。两种类型的修复都与基因组的改变有关。由于这通常是不可取的，因此这些维修模式可能被视为“最后的修复”。这里提出的工作将调查对端粒损失的种系反应。目标是确定用于检测和消除这种损害形式的细胞的遗传控制。将探索男性和女性种系之间的反应差异。这里提出的实验还将研究BIR修复模式，以前在任何种系中都没有证明这一点。这种类型的维修具有更多的兴趣，因为它与某些癌细胞中的端粒维持形式相似。