Surrallés J, Puerto S, Ramírez M J, Creus A, Marcos R, Mullenders L H, Natarajan A T
Group of Mutagenesis, Genetics Unit, Department of Genetics and Microbiology, Edifici Cn, Universitat Autònoma de Barcelona, 08193 Bellaterra, Cerdanyola del Vallès, Barcelona, Spain.
Mutat Res. 1998 Aug 3;404(1-2):39-44. doi: 10.1016/s0027-5107(98)00093-1.
This paper is a brief overview of the studies we have recently conducted to unravel how chromatin structure and DNA repair modulate the fragility of diverse chromosomes and chromosomal regions. We have employed a combination of molecular cytogenetic techniques, including interphase and metaphase multicolour FISH, reverse FISH with CpG-rich probes or repaired DNA fractions, and several combinations of FISH and immunocytogenetics with antibodies against acetylated histones. The targets of our investigation were human constitutive and facultative heterochromatin, chromosomes with high and low gene density and human and hamster fragile sites. The role of DNA repair was investigated by using DNA repair deficient mutants and DNA repair inhibitors. We found that intragenomic heterogeneity in DNA repair and chromatin structure may explain a substantial part of the differential fragility of diverse chromosomes and chromosomal regions.
本文简要概述了我们最近开展的一些研究，这些研究旨在阐明染色质结构和DNA修复如何调节不同染色体及染色体区域的易碎性。我们采用了多种分子细胞遗传学技术，包括间期和中期多色荧光原位杂交（FISH）、使用富含CpG的探针或修复后的DNA片段进行反向FISH，以及FISH与针对乙酰化组蛋白抗体的免疫细胞遗传学的多种组合。我们的研究对象包括人类组成型和兼性异染色质、基因密度高和低的染色体以及人类和仓鼠的脆性位点。通过使用DNA修复缺陷突变体和DNA修复抑制剂来研究DNA修复的作用。我们发现，DNA修复和染色质结构的基因组内异质性可能解释了不同染色体及染色体区域易碎性差异的很大一部分原因。
