유전적 불안정성 과 세포 사멸사

• 영문명: Genomic Instability and Apoptosis
• 발행기관: 조선대학교 의학연구원
• 저자명: 김승곤(Seung-Gon Kim) 황걸(Gul Hwang)
• 간행물 정보: 『The Medical Journal of Chosun University』제33권 제2호, 7~14쪽, 전체 8쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2008.06.30

영문 초록

Genome integrity and cell proliferation and survival are regulated by an intricate network of pathways that include cell-cycle checkpoints, DNA repair and recombination, and program m ed cell death. Permanent or transient genomic instability, which represents one of the fundamental characteristics of cancer, might be ascribed to deficiencies in numerous cellular processes including mitotic-checkpoint regulation, and DNA damage signalling and repair, as well as telomere maintenance and centrosome function. This review will focus on the complex interplay between genomic instability and apoptosis regulation that participates in carcinogenesis. The relationship between genomic integrity and cell-death regulation can follow at least three different non-exclusive patterns, all of which might be important for the development of cancer. First, genomic instability can lead to the mutation, or altered expression levels, of cell-death regulators. Second, disabled apoptosis can favor genomic instability. Indeed, numerous cellular mechanisms enforce the rule ’better dead than wrong , which means that cells that have a damaged genome or are afflicted by many disorders will be aborted by apoptosis - thereby avoiding the propagation of potentially oncogenic mutations. DNA double-strand breaks (DSBs), telomere dysflinction, illicit polyploidy or abnormal mitoses can directly trigger apoptosis through a default pathway. However, if apoptosis is inhibited for some reason, this increases the risk of chromosomal instability (CIN) at several levels, and cells that are sufficiently fit to survive can be at a growth advantage, which can lead to cancer. Third, a single protein or process might be involved in the control of both apoptosis and genomic instability, which allows crosstalk between the processes. Here, we will discuss these different possibilities, their molecular mechanisms and their possible impact on carcinogenesis.

목차

유전적 불안정성: 세포 사멸사의 이상

DNA 손상후 세포사멸사에 의한 염색체적 불안정성 (CIN rChromosomal instability) 억제

Telomere 불안정성과 사멸사

배수성 조절과 사멸사

p53에 의한 사멸사 대 세포주기의 조절

세포사멸사와 DNA수복의 상호관계성

결론 및 전망