Unwinding protein complexes in ALTernative telomere maintenance.

Unwinding protein complexes in ALTernative telomere maintenance.
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DOI:
10.1002/jcb.22388
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发表时间:
2010-01-01
影响因子:
4
通讯作者:
Groden, Joanna
Groden, Joanna
中科院分区:
生物学2区
文献类型:
--
作者:
Bhattacharyya, Saumitri;Sandy, April;Groden, Joanna

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端粒由特殊染色质组成,其中包括 DNA 修复/重组蛋白、端粒 DNA 结合蛋白和许多三维核酸结构(包括 G 四联体和 D 环)。许多研究表明,BLM 和 WRN recQ 样解旋酶在重组介导的端粒延长或端粒选择性延长 (ALT) 机制(在端粒酶缺失的情况下维持/延长端粒的过程)中发挥重要作用。 BLM 和 WRN 定位于端粒酶阴性永生化细胞系中 ALT 相关核体内,并与端粒特异性蛋白 POT1、TRF1 和 TRF2 相互作用。解旋酶活性受这些相互作用的调节。 BLM 在 DNA 双链断裂修复过程中发挥作用,例如非同源末端连接、同源重组介导的修复、停滞复制叉的解析和合成依赖性链退火,尽管其在端粒上的精确功能是推测的。 WRN 还在 DNA 复制、重组和修复中发挥作用,除了其解旋酶结构域之外,还包括其他 recQ 样解旋酶中未发现的核酸外切酶结构域。因此,BLM 和 WRN 的生化特性在 DNA 复制、重组和修复以外的生物过程中很重要。在这篇综述中,我们讨论了人类 rec-Q 样解旋酶的一些先前和最近的发现及其在 ALT 过程中端粒伸长中的作用。
Telomeres are composed of specialized chromatin that includes DNA repair/recombination proteins, telomere DNA-binding proteins and a number of three dimensional nucleic acid structures including G-quartets and D-loops. A number of studies suggest that the BLM and WRN recQ-like helicases play important roles in recombination-mediated mechanisms of telomere elongation or Alternative Lengthening of Telomeres (ALT), processes that maintain/elongate telomeres in the absence of telomerase. BLM and WRN localize within ALT-associated nuclear bodies in telomerase-negative immortalized cell lines and interact with the telomere-specific proteins POT1, TRF1 and TRF2. Helicase activity is modulated by these interactions. BLM functions in DNA double-strand break repair processes such as non-homologous end joining, homologous recombination-mediated repair, resolution of stalled replication forks and synthesis-dependent strand annealing, although its precise functions at the telomeres are speculative. WRN also functions in DNA replication, recombination and repair, and in addition to its helicase domain, includes an exonuclease domain not found in other recQ-like helicases. The biochemical properties of BLM and WRN are, therefore, important in biological processes other than DNA replication, recombination and repair. In this review, we discuss some previous and recent findings of human rec-Q-like helicases and their role in telomere elongation during ALT processes.
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