Schematic illustration of the proposed/expected mechanism of the effects of CC3/TIP30 on responses to DNA damage. The scheme illustrates changes in expression of thee proteins involved in DNA damage responses depending on changes in levels of CC3. Changes in protein levels are represented as increases/decreases in the font size or thickness compared to the uniform size of font used for all proteins in the middle part of the scheme ("CC3/TIP30 unchanged") prior to UV treatment. Overexpression of CC3 (top part) leads to higher levels of c-FOS and lower levels of p21 and DDB2, while silencing of CC3 has no effect on c-FOS in untreated cells, but significantly increases levels of DDB2 and p21CIP. After exposure to UV cells expressing exogenous CC3 protein fail to increase levels of FOS and p21CIP. They also accumulate less p21CIP in their nuclei after UV exposure (Figure 5D). This could contribute to the deficiency in repair of DNA damage. Cells where CC3 expression is silenced (lower part. "CC3/TIP30 KD) continue to maintain the already higher levels of p21CIP without further increasing it. More of these cells have nuclear p21 (Figure 5E). They also show a higher increase in the levels of FOS after UV exposure. Altogether, these changes observed after CC3 knockdown have minor consequences for the repair of DNA damage, but significantly inhibit DNA translesion synthesis (TLS) after DNA damage likely due to high levels of p21CIP.
Fong et al. BMC Cell Biology 2010 11:23 doi:10.1186/1471-2121-11-23