Department of Biochemistry and Microbiology, University of Victoria, BC, Canada.
Bioessays. 2010 Jan;32(1):51-9. doi: 10.1002/bies.200900089.
Base pair mismatches in DNA arise from errors in DNA replication, recombination, and biochemical modification of bases. Mismatches are inherently transient. They are resolved passively by DNA replication, or actively by enzymatic removal and resynthesis of one of the bases. The first step in removal is recognition of strand discontinuity by one of the MutS proteins. Mismatches arising from errors in DNA replication are repaired in favor of the base on the template strand, but other mismatches trigger base excision or nucleotide excision repair (NER), or non-repair pathways such as hypermutation, cell cycle arrest, or apoptosis. We argue that MutL homologues play a key role in determining biologic outcome by recruiting and/or activating effector proteins in response to lesion recognition by MutS. We suggest that the process is regulated by conformational changes in MutL caused by cycles of ATP binding and hydrolysis, and by physiologic changes which influence effector availability.
DNA 中的碱基配对错误源于 DNA 复制、重组和碱基生化修饰过程中的错误。碱基错配本质上是瞬时的。它们可以通过 DNA 复制被动解决，也可以通过酶促去除和其中一个碱基的重新合成来主动解决。去除的第一步是由 MutS 蛋白之一识别链的不连续性。复制过程中出现的碱基错误被修复以利于模板链上的碱基，但其他碱基错配会引发碱基切除或核苷酸切除修复 (NER)，或非修复途径，如超突变、细胞周期停滞或细胞凋亡。我们认为，MutL 同源物通过响应 MutS 对损伤的识别，招募和/或激活效应蛋白，在决定生物学结果方面发挥着关键作用。我们提出，该过程受 MutL 构象变化的调节，这种构象变化是由 ATP 结合和水解循环引起的，也受影响效应蛋白可用性的生理变化调节。
