Santucci-Darmanin Sabine, Paquis-Flucklinger Véronique
Equipe M3R, LRC CEA no. 32-V, UMR Cnrs UNSA 6549, Faculté de Médecine, avenue de Valombrose, 06107 Nice, France.
Med Sci (Paris). 2003 Jan;19(1):85-91. doi: 10.1051/medsci/200319185.
In eukaryotes, homologs of the Escherichia coli MutS and MutL proteins are crucial for both meiotic recombination and post-replicative DNA mismatch repair. Both pathways require the formation of a MutS homolog complex which interacts with a second heterodimer, composed of two MutL homologs. During mammalian meiosis, it is likely that chromosome synapsis requires the presence of a MSH4-MSH5 heterodimer. PMS2, a MutL homolog, seems to play an important role in this process. A MSH4-MSH5 heterodimer is also likely present later with other MutL homologs (MLH1 and MLH3) and is involved in the crossing-over process. The phenotype of msh4-/- mutant mice and MSH4 immunolocalization on meiotic chromosomes suggest that MSH4 has an early function in mammalian meiotic recombination. Both MSH4 and PMS2 directly interact with the RAD51 DNA strand exchange protein. In addition, MSH4 and RAD51 proteins co-localize on mouse meiotic chromosome cores. These results suggest that MSH4 and its partners could act, just after strand exchange promoted by RAD51, to check the homology of DNA heteroduplexes.
在真核生物中，大肠杆菌MutS和MutL蛋白的同源物对于减数分裂重组和复制后DNA错配修复都至关重要。这两条途径都需要形成一个MutS同源物复合物，该复合物与由两个MutL同源物组成的第二个异二聚体相互作用。在哺乳动物减数分裂过程中，染色体联会可能需要MSH4-MSH5异二聚体的存在。MutL同源物PMS2似乎在这个过程中起重要作用。MSH4-MSH5异二聚体在后期也可能与其他MutL同源物（MLH1和MLH3）一起存在，并参与交叉过程。msh4-/-突变小鼠的表型以及MSH4在减数分裂染色体上的免疫定位表明，MSH4在哺乳动物减数分裂重组中具有早期功能。MSH4和PMS2都直接与RAD51 DNA链交换蛋白相互作用。此外，MSH4和RAD51蛋白在小鼠减数分裂染色体核心上共定位。这些结果表明，MSH4及其伙伴可能在RAD51促进链交换之后立即发挥作用，以检查DNA异源双链体的同源性。
