Table 1 Comparison of the main features of RFWD3, PRP19, and HERC2.
RFWD3 | PRP19 | HERC2 | |
|---|---|---|---|
RPA interaction timing | Constitutive At stalled fork | After genotoxic stress Hyperphosphorylated RPA2 | Constitutive Dissociates after damage |
RPA interaction situation | ssDNA-bound RPA | ssDNA-bound RPA | ssDNA-unbound RPA |
Effect of knockdown on RPA2 phosphorylation | pS33↓, pS4/8↓, pT21↓(short) pS33↑, pS4/8↑ (long MMC) | pS33↓, pS4/8↓, pT21↓ | pS33↓, pS4/8↓, pT21↓ (low stress) pS4/8→, pT21 → (high stress) |
Effect of E3 domain deletion on RPA2 phosphorylation | NA | NA | pS33↑ |
Effect of knockdown on Chk1 phosphorylation | pS317-Chk1↓ (early after stress) pS317-Chk1→ | pS345-Chk1↓ | pS317-Chk1↑ (early after stress) pS317-Chk1→ |
RPA2 modification for ubiquitination | Hyperphosphorylated RPA2 | Hyperphosphorylated RPA2 | Ser33 phosphorylated RPA2 |
Trigger for ubiquitination | Genotoxic stress | Genotoxic stress | Without stress |
Effect of ATR inhibition | Elevates RPA2 ubiquitination (after stress) | Dissociates from RPA | Inhibits RPA2 ubiquitination |
Signal by ubiquitination | Non-degradation Degradation (long exposure to MMC) | Non-degradation | Degradation |
Consequences of dysfunction | Failure in HR, fork restart, ICLR | Failure in HR, fork restart | Accumulation of G4, SCE |
