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端粒、间质端粒重复序列和染色体畸变。

Telomeres, interstitial telomeric repeat sequences, and chromosomal aberrations.

作者信息

Bolzán Alejandro D, Bianchi Martha S

机构信息

Laboratorio de Citogenética y Mutagénesis, Instituto Multidisciplinario de Biología Celular (IMBICE), C.C. 403, 1900 La Plata, Argentina.

Laboratorio de Citogenética y Mutagénesis, Instituto Multidisciplinario de Biología Celular (IMBICE), C.C. 403, 1900 La Plata, Argentina.

出版信息

Mutat Res. 2006 Jun;612(3):189-214. doi: 10.1016/j.mrrev.2005.12.003. Epub 2006 Feb 21.

Abstract

Telomeres are specialized nucleoproteic complexes localized at the physical ends of linear eukaryotic chromosomes that maintain their stability and integrity. The DNA component of telomeres is characterized by being a G-rich double stranded DNA composed by short fragments tandemly repeated with different sequences depending on the species considered. At the chromosome level, telomeres or, more properly, telomeric repeats--the DNA component of telomeres--can be detected either by using the fluorescence in situ hybridization (FISH) technique with a DNA or a peptide nucleic acid (PNA) (pan)telomeric probe, i.e., which identifies simultaneously all of the telomeres in a metaphase cell, or by the primed in situ labeling (PRINS) reaction using an oligonucleotide primer complementary to the telomeric DNA repeated sequence. Using these techniques, incomplete chromosome elements, acentric fragments, amplification and translocation of telomeric repeat sequences, telomeric associations and telomeric fusions can be identified. In addition, chromosome orientation (CO)-FISH allows to discriminate between the different types of telomeric fusions, namely telomere-telomere and telomere-DNA double strand break fusions and to detect recombination events at the telomere, i.e., telomeric sister-chromatid exchanges (T-SCE). In this review, we summarize our current knowledge of chromosomal aberrations involving telomeres and interstitial telomeric repeat sequences and their induction by physical and chemical mutagens. Since all of the studies on the induction of these types of aberrations were conducted in mammalian cells, the review will be focused on the chromosomal aberrations involving the TTAGGG sequence, i.e., the telomeric repeat sequence that "caps" the chromosomes of all vertebrate species.

摘要

端粒是位于线性真核染色体物理末端的特殊核蛋白复合物,可维持其稳定性和完整性。端粒的DNA成分的特征是富含G的双链DNA,由短片段串联重复组成,其序列因所考虑的物种而异。在染色体水平上,端粒,或者更确切地说,端粒重复序列(端粒的DNA成分),可以通过使用荧光原位杂交(FISH)技术,用DNA或肽核酸(PNA)端粒探针进行检测,即该探针可同时识别中期细胞中的所有端粒,也可以通过使用与端粒DNA重复序列互补的寡核苷酸引物的引物原位标记(PRINS)反应来检测。使用这些技术,可以识别不完整的染色体元件、无着丝粒片段、端粒重复序列的扩增和易位、端粒关联和端粒融合。此外,染色体定向(CO)-FISH可以区分不同类型的端粒融合,即端粒-端粒融合和端粒-DNA双链断裂融合,并检测端粒处的重组事件,即端粒姐妹染色单体交换(T-SCE)。在本综述中,我们总结了目前关于涉及端粒和间质端粒重复序列的染色体畸变及其由物理和化学诱变剂诱导的知识。由于所有关于这些类型畸变诱导的研究都是在哺乳动物细胞中进行的,因此本综述将重点关注涉及TTAGGG序列的染色体畸变,即“覆盖”所有脊椎动物物种染色体的端粒重复序列。

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