Table 3.
Correlation between experimental validations and nodes in the FA/BRCA BNM
| Process | Nodes in the | Experimental markers | Validated role | References |
|---|---|---|---|---|
| FA/BRCA BNM | used in this study | in the BNM | ||
| DNA damage | ICL | MMC | FA cells are | [21, 25, 26] |
| induction | hypersensitive | |||
| to ICL inducing | ||||
| agents | ||||
| Upstream | FAcore | Non-evaluated | ICL recognition | [14, 16, 17] |
| FA/BRCA | FANCD2I | proteins | ||
| pathway | NUC1 | |||
| NUC2 | ||||
| DNA repair | ADD | γH2AX, | ICLs are unhooked | [13, 21] |
| intermediaries | DSB | CA in metaphase | by FA core-recruited | |
| spreads | DNA-endonucleases | |||
| that generate a DSB | ||||
| and an ADD | ||||
| Downstream | TLS | Non-evaluated | The ADD and DSB | [14, 15, 18, 54] |
| FA/BRCA | FAHRR | are repaired by TLS | ||
| pathway | and FA-dependent | |||
| downstream homologous | ||||
| recombination repair, | ||||
| respectively. FA cells | ||||
| accumulate DSBs | ||||
| Alternative | HRR2 | Non-evaluated | FA cells use | [49, 56] |
| DNA repair | NHEJ | alternative DNA | ||
| pathways | repair pathways, | |||
| mainly NHEJ | ||||
| HRR2 is a | ||||
| criptic repair choice | ||||
| Checkpoint | ATR | Cell cycle arrest | Upon DNA damage | [27, 28, 31] |
| ATM | in G2, pCHK1-S341, | normal and FA | ||
| p53 | p21 gene expression, | cells activate | ||
| MYT1, WEE1, p21 | the G2/M checkpoint | |||
| proteins | ||||
| Checkpoint | CHKREC | MPM2 mitotic index, | The checkpoint | [83, 84] and this work |
| recovery | cytokinesis block assay, | is inactivated by | ||
| G2/M transcriptional | CHKREC after | |||
| program, WIP1, PLK1, | DNA repair | |||
| CDC25, Aurora A | FA cells seem to have | |||
| proteins | a lower threshold for | |||
| CHKREC activation | ||||
| compared to normal cells |