The Fanconi anemia core complex associates with chromatin during S phase
The Fanconi anemia core complex associates with chromatin during S phase
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DOI：
10.1182/blood-2004-01-0001
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发表时间：
2005-01-15
期刊：
影响因子：
20.3
通讯作者：
Kupfer, GM
中科院分区：
文献类型：
--
作者：
Mi, J;Kupfer, GM
范可尼贫血 (FA) 是一种常染色体隐性遗传疾病，以骨髓衰竭、出生缺陷和癌症为特征。 FA 蛋白 FANCA、FANCC、FANCE、FANCF、FANCG 和 FANCL 参与核心复合体。我们之前已经证明，该复合体的几个成员在有丝分裂之前与染色质结合，并且这种结合在 DNA 损伤后增强。本研究的目的是确定细胞质和核区室之间复杂运动的动力学。 FANCA、FANCC 和 FANCG 的荧光标记版本共定位于细胞质和细胞核，主要是染色质。在 G(1)-S 边界，FA 核心复合体作为染色质上的焦点存在，逐渐扩散并迁移到核外围，并通过有丝分裂完全从浓缩染色体中排除。染色质纤维分析显示 FA 蛋白在 G(1)-S 和 S 期沿染色质纤维广泛染色。 DNA 交联剂丝裂霉素 C 处理会导致病灶扩散，并增加复杂蛋白与染色质的结合。以及与染色质纤维的复杂结合的扩散和增加。这些数据与 FA 蛋白在 S 期在染色质水平上发挥作用以调节和维持基因组稳定性的观点一致。 (C) 2005 年，美国血液学会。
Fanconi anemia (FA) is an autosomal recessive disease marked by bone marrow failure, birth defects, and cancer. The FA proteins FANCA, FANCC, FANCE, FANCF, FANCG, and FANCL participate in a core complex. We previously have shown that several members of this complex bind to chromatin until mitosis and that this binding increases after DNA damage. The purpose of the present study was to determine the dynamics of complex movement between cytoplasm and nuclear compartments. Fluorescent-tagged versions of FANCA, FANCC, and FANCG colocalize in cytoplasm and nucleus, chiefly in chromatin. At the G(1)-S border, the FA core complex exists as foci on chromatin, progressively diffusing and migrating to the nuclear periphery and becoming completely excluded from condensed chromosomes by mitosis. Chromatin fiber analysis shows FA proteins diffusely staining along chromatin fibers during G(1)-S and S phase. Treatment with the DNA cross-linker mitomycin C results in a diffusion of foci and increased binding of complex proteins to chromatin. as well as diffuse and increased complex binding to chromatin fibers. These data are consistent with the idea that the FA proteins function at the level of chromatin during S phase to regulate and maintain genomic stability. (C) 2005 by The American Society of Hematology.