Localization of MLH3 at the Centrosomes

Abstract

Mutations in human DNA mismatch repair (MMR) genes are commonly associated with hereditary nonpolyposis colorectal cancer (HNPCC). MLH1 protein heterodimerizes with PMS2, PMS1, and MLH3 to form MutLα, MutLβ, and MutLγ, respectively. We reported recently stable expression of GFP-linked MLH3 in human cell lines. Monitoring these cell lines during the cell cycle using live cell imaging combined with confocal microscopy, we detected accumulation of MLH3 at the centrosomes. Fluorescence recovery after photobleaching (FRAP) revealed high mobility and fast exchange rates at the centrosomes as it has been reported for other DNA repair proteins. MLH3 may have a role in combination with other repair proteins in the control of centrosome numbers.

Mitotic abnormalities precede microsatellite instability in lynch syndrome-associated colorectal tumourigenesis

“… 63 MMR proteins MLH3 and MSH2 are involved in the regulation of chromosome distribution by controlling the number of centrosomes. 64 , 65 Our findings, mostly derived from MLH1 mutation carriers, suggest similar role for MLH1. According to GOrilla, the regulation of centriole replication, centrosome duplication, and centrosome cycle regulation were all altered (gene expression decreased) in LS mucUA ( Supplementary Table S2 ).…”

A spontaneous mutation in MutL‐Homolog 3 (HvMLH3) affects synapsis and crossover resolution in the barley desynaptic mutant des10

“…d). This would suggest that our observations are unlike the association with heterochromatic repeats found in mouse (Baker et al ., ) or with chromatin organization suggested during chromosome segregation in humans (Roesner et al ., ). This would therefore indicate that MLH3 is recruited earlier to the newly formed axes potentially during synapsis, rather than on mature chromosomes axes, as suggested by animal studies reporting the presence of MLH3 at pachynema.…”

Gene Expression, DNA Methylation and Prognostic Significance of DNA Repair Genes in Human Bladder Cancer

“…Inactivation of MLH1 has also been observed in sporadic cancers like gastric cancer [36], ovarian cancer [37], non-small cell lung carcinoma (NSCLC) [38], bladder cancer [39] and many other types of cancer. In MMR system, MLH1 forms a heterodimer with PMS2 (known as MutLα) or with MLH3 (known as MutLγ) which can be observed in meiotic recombination events [40]. In addition, studies in the mouse model have shown that MLH1/MLH3 heterodimer may be involved in the repair of base-base mismatches and small insertion/deletion loops [41].…”