An ACF1-ISWI chromatin-remodeling complex is required for DNA replication through heterochromatin
An ACF1-ISWI chromatin-remodeling complex is required for DNA replication through heterochromatin
复制标题
DOI：
10.1038/ng1046
复制
发表时间：
2002-12-01
期刊：
影响因子：
30.8
通讯作者：
Varga-Weisz, PD
中科院分区：
文献类型：
--
作者：
Collins, N;Poot, RA;Varga-Weisz, PD
人们对真核 DNA 复制机制穿透浓缩染色质结构以复制底层 DNA 的机制知之甚少。在这里，我们提供的证据表明，ACF1-ISWI 染色质重塑复合物是哺乳动物细胞中通过异染色质复制所必需的。 ACF1（利用 ATP 的染色质组装和重塑因子 1）和 ISWI 同工型 SNF2H（蔗糖非发酵 2 同源物）在复制着丝粒周围异染色质方面特别富集。 RNAi 介导的 ACF1 损耗会特异性损害着丝粒周围异染色质的复制。因此，ACF1 的消耗会导致细胞周期进展延迟至 S 期后期。体内 SNF2H 的缺失会减慢整个 S 期 DNA 复制的进程，表明与 ACF1 的功能重叠。用 5-aza-2-deoxycytidine 解凝异染色质可逆转 ACF1 和 SNF2H 消耗的影响。不能与 SNF2H 相互作用的 ACF1 突变体的表达也会干扰浓缩染色质的复制。我们的数据表明，ACF1-SNF2H 复合物是一种专用机制的一部分，该机制使 DNA 通过高度浓缩的染色质区域进行复制。
The mechanism by which the eukaryotic DNA-replication machinery penetrates condensed chromatin structures to replicate the underlying DNA is poorly understood. Here we provide evidence that an ACF1-ISWI chromatin-remodeling complex is required for replication through heterochromatin in mammalian cells. ACF1(ATP-utilizing chromatin assembly and remodeling factor 1) and an ISWI isoform, SNF2H (sucrose nonfermenting-2 homolog), become specifically enriched in replicating pericentromeric heterochromatin. RNAi-mediated depletion of ACF1 specifically impairs the replication of pericentromeric heterochromatin. Accordingly, depletion of ACF1 causes a delay in cell-cycle progression through the late stages of S phase. In vivo depletion of SNF2H slows the progression of DNA replication throughout S phase, indicating a functional overlap with ACF1. Decondensing the heterochromatin with 5-aza-2-deoxycytidine reverses the effects of ACF1 and SNF2H depletion. Expression of an ACF1 mutant that cannot interact with SNF2H also interferes with replication of condensed chromatin. Our data suggest that an ACF1-SNF2H complex is part of a dedicated mechanism that enables DNA replication through highly condensed regions of chromatin.