Laboratory of Genomic Integrity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-3371, USA.
Nucleic Acids Res. 2013 Feb 1;41(3):1649-60. doi: 10.1093/nar/gks1277. Epub 2012 Dec 16.
Human DNA polymerases η and ι are best characterized for their ability to facilitate translesion DNA synthesis (TLS). Both polymerases (pols) co-localize in 'replication factories' in vivo after cells are exposed to ultraviolet light and this co-localization is mediated through a physical interaction between the two TLS pols. We have mapped the polη-ι interacting region to their respective ubiquitin-binding domains (UBZ in polη and UBM1 and UBM2 in polι), and demonstrate that ubiquitination of either TLS polymerase is a prerequisite for their physical and functional interaction. Importantly, while monoubiquitination of polη precludes its ability to interact with proliferating cell nuclear antigen (PCNA), it enhances its interaction with polι. Furthermore, a polι-ubiquitin chimera interacts avidly with both polη and PCNA. Thus, the ubiquitination status of polη, or polι plays a key regulatory function in controlling the protein partners with which each polymerase interacts, and in doing so, determines the efficiency of targeting the respective polymerase to stalled replication forks where they facilitate TLS.
人类 DNA 聚合酶 η 和 ι 的特点是能够促进跨损伤 DNA 合成 (TLS)。细胞暴露在紫外线下后，两种聚合酶（pols）在“复制工厂”中共定位，这种共定位是通过两种 TLS pols 之间的物理相互作用介导的。我们已经将 polη-ι 相互作用区域映射到它们各自的泛素结合结构域（polη 中的 UBZ 和 polι 中的 UBM1 和 UBM2），并证明泛素化任一种 TLS 聚合酶都是它们物理和功能相互作用的先决条件。重要的是，虽然 polη 的单泛素化会阻止其与增殖细胞核抗原 (PCNA) 相互作用，但它会增强其与 polι 的相互作用。此外，polι-泛素嵌合体与 polη 和 PCNA 都有强烈的相互作用。因此，polη 或 polι 的泛素化状态在控制每种聚合酶与之相互作用的蛋白质伴侣方面起着关键的调节作用，并通过这种方式，决定了将各自的聚合酶靶向停滞复制叉的效率，在那里它们促进 TLS。
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