POLI介导的跨损伤合成
中文名称
通路描述
POLI是一种Y家族DNA聚合酶，其活性位点倾向于Hoogsteen碱基配对而非Watson-Crick碱基配对。POLI介导的Hoogsteen碱基配对和模板嘌呤从anti构象旋转至syn构象，作为机制以置换模板G或模板A上的加合物，干扰DNA复制，或允许受损嘌呤与Watson-Crick边缘断裂但Hoogsteen边缘完整进行碱基配对（Nair et al. 2004, Nair et al. 2006）。POLI通过与PCNA和REV1相互作用招募至DNA损伤位点。POLI含有PIP盒和两个UBM（泛素结合基序），负责POLI与泛素化修饰的PCNA（MonoUb:K164-PCNA）结合（Bienko et al. 2005, Haracska et al. 2005, Bomar et al. 2010）。POLI与REV1 C端之间的相互作用在进化上保守（Kosarek et al. 2003, Guo et al. 2003, Ohashi et al. 2004）。在POLI介导的跨损伤DNA合成后，它掺入与受损模板碱基相对的dNMP后无法有效延伸DNA链。延伸步骤由聚合酶ζ复合物（POLZ）执行，该复合物由REV3L和MAD2L2亚基组成（Johnson et al. 2000）。REV1和POLZ在POLI介导的跨损伤DNA合成中的参与表明，POLI与REV1和POLZ形成四级复合物，正如POLK所示，并推测适用于其他Y家族DNA聚合酶（Xie et al. 2012）。
英文描述
Translesion synthesis by POLI DNA polymerase iota (POLI) is a Y family DNA polymerase with an active site that favours Hoogsteen base pairing instead of Watson-Crick base pairing. POLI-mediated Hoogsteen base pairing and rotation of template purines from anti to syn conformation serves as a mechanism to displace adducts on template G or template A that interfere with DNA replication, or to allow base pairing of damaged purines with a disrupted Watson-Crick edge but an intact Hoogsteen edge (Nair et al. 2004, Nair et al. 2006).POLI is recruited to DNA damage sites through its interaction with PCNA and REV1. POLI contains a PIP box and two UBMs (ubiquitin binding motifs) that are responsible for POLI binding to monoubiquitinated PCNA (MonoUb:K164-PCNA) (Bienko et al. 2005, Haracska et al. 2005, Bomar et al. 2010). The interaction between POLI and the C-terminus of REV1 is evolutionarily conserved (Kosarek et al. 2003, Guo et al. 2003, Ohashi et al. 2004).After it incorporates a dNMP opposite to damaged template base, POLI is unable to efficiently elongate the DNA strand further. The elongation step is performed by the polymerase zeta complex (POLZ), composed of REV3L and MAD2L2 subunits (Johnson et al. 2000). The involvement of REV1 and POLZ in POLI-mediated translesion DNA synthesis (TLS) suggests that POLI forms a quaternary complex with REV1 and POLZ, as shown for POLK and proposed for other Y family DNA polymerases (Xie et al. 2012).
所含基因
17 个基因