错配修复 (MMR) 由 MSH2:MSH3 (MutSbeta) 引导
中文名称
通路描述
MSH2:MSH3 (MutSbeta) 结合未配对的双核苷酸环 (Palombo et al. 1996, Genschel et al. 1998)。人类细胞中 MSH2:MSH6 的 MSH2:MSH3 (MutSbeta) 比例约为 6 倍，比例失衡可导致突变表型 (Drummond et al. 1997, Marra et al. 1998)。错配修复激活 MSH2:MSH3 将 ADP 交换为 ATP，采取构象以允许其在 DNA 上移动，并与下游效应物 PCNA、MLH1:PMS2 和 EXO1 相互作用。与 PCNA 的相互作用启动新复制链的切除。MLH1:PMS2 在 EXO1 的作用下使切口扩大为数百个核苷酸的缺口。DNA 聚合酶 delta 跨越缺口进行聚合，剩余的切口由 DNA 连接酶 I 封闭。
英文描述
Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta) MSH2:MSH3 (MutSbeta) binds unpaired loops of 2 or more nucleotides (Palombo et al. 1996, Genschel et al. 1998). Human cells contain about 6-fold more MSH2:MSH6 than MSH2:MSH3 (MutSbeta) and an imbalance in the ratio can cause a mutator phenotype (Drummond et al. 1997, Marra et al. 1998). Binding of the mismatch activates MSH2:MSH3 to exchange ADP for ATP, adopt the conformation to allow movement along the DNA, and interact with downstream effectors PCNA, MLH1:PMS2 and EXO1. The interaction with PCNA initiates excision of the recently replicated strand. MLH1:PMS2 makes a nick that is enlarged to a gap of hundreds of nucleotides by EXO1. DNA is polymerized across the gap by DNA polymerase delta and the remaining nick is sealed by DNA ligase I.
所含基因
14 个基因