Complementation groups

Zhou W, Gurubhagavatula S, Liu G et al. Excision repair cross-complementation group 1 polymorphism predicts overall survival in advanced non-small-cell lung cancer patients treated with platinum-based chemotherapy. Clin Cancer Res 2004 10 4939 943. 

Probably nearly 200 rodent mutant lines have now been isolated and tested by genetic complementation for their genetic identity. Complementation at first involved cell-fusion techniques and this finally established the existence of 11 complementation groups, each representing a single gene. 

A fourth type of WgaR CHO cell mutant has now been isolated (Stanley, manuscript in preparation). This mutant is more highly resistant to WGA than the previously described mutants and it has been shown to belong to a new complementation group (group VIII). 

One problem associated with the yeast 2-hybrid system is that protein interactions that are dependent on posttranslational modifications that can occur only in mammalian cells, would not be detected. For example, monoubiquitinylation and serine phosphorylation of a Fanconi anemia complementation group D2 protein (FANC-D2) are both required for mediating cellular resistance to ionizing radiation (122), an interaction that would be missed using this approach. 

The same logic was used to identify the groups of mutants who allowed the growth of other mutants, or who were able to grow on the compounds excreted by other groups of mutants. In the case of tryptophan, five such complementation groups existed. 

From these data, it should be fairly easy to deduce that complementation group E comes last in the pathway while complementation group A comes first. 

This did not establish the pathway completely. The next step was to identify the compounds that are excreted and allow growth of the other mutants. Next, the pathway was established biochemically by identifying and purifying the individual proteins that carry out the steps corresponding to each complementation group, showing that the enzymes behaved kinetically in the way that the other analyses predicted was necessary. These studies showed that the proteins... 

Cava, J.R., Tao, H., Noel, K.D. Mapping of complementation groups within a Rhizobium legu-minosarum CFN42 chromosomal region required for lipopolysaccharide synthesis. Mol Gen Genetics 221 (1990) 125-128. 

Figure 55-2 Multi-analyte approach to the prenatal diagnosis of methylmalonic acidemia (cb/C complementation group) by metabolite analysis in ceil-free supernatant of amniotic fluid collected at 16 weeks of gestational age. The symbol marks internal standards. A, Determination of total homocysteine by LC-MS/MS (selected reaction monitoring, SRM, transition m/z 136 to m/z 90 and m/z 140 to m/z 94 for the d -labeled internal standard). The concentration of total homocysteine was l5.7pmol/L (0.7 to 2.0pmol/L). B, Determination of methylmalonic acid by LC-MS/MS (SRM, transition m/z 231 to m/z 119 and m/z 234 to m/z 122 for the d3-labeled internal standard). The concentration of methylmalonic acid was 8.7pmol/L, the reference interval for 16 to 19 weeks of gestational age is 0.2 to 0.7)j,mol/L. C, Determination of propionylcarnitine by LC-MS/MS (parent of m/z 85 scan, the [M+H] ion of C3 is m/z 274, m/z 277 for the interna standard). The concentration was 5.6pmol/L (i.5 to l.8pmoi/L),the C3/C4 ratio was 6.9 (0.9 to 2.6).

Seo BG, Kwon HC, Oh SY et al (2009) Comprehensive analysis of excision repair complementation group 1, glutathione S-transferase, thymidylate synthase and uridine diphosphate glucuronosyl transferase 1A1 polymorphisms predictive for treatment outcome in patients with advanced gastric cancer treated with FOLFOX or FOLFIBI. Oncol Rep 22 127-136... 

Complementation analyses and molecular studies have had a profound effect on the classification and conceptual framework of the PBD. Table 2 lists the main clinical features and relative frequencies of the PBD. Note that the ZS, NATD, and IRD phenotypes can be associated with 11 different complementation groups and with 9 different molecular defects. This finding forms the basis for the conclusion that these three phenotypes represent a continuum, rather than distinct disease entities. In contrast, among the PBD, RCDP is associated only with a defect in Pex7. 

Moser AB, Rasmussen M, Naidu S, Watkins PA, McGuinness M, Hajra AK. el al. Phenotypeof patients with peroxisomal disorders subdivided into sixteen complementation groups.. 1 Pediatr 1995 127(1) 13-22. 

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