hMSH2 Recruits ATR to DNA Damage Sites for Activation during DNA Damage-induced Apoptosis*

PARP-2 domain requirements for DNA damage-dependent activation and localization to sites of DNA damage.

Poly(ADP-ribose) polymerase-2 (PARP-2) is one of three human PARP enzymes that are potently activated during the cellular DNA damage response (DDR). DDR-PARPs detect DNA strand breaks, leading to a dramatic increase in their catalytic production of the posttranslational modification poly(ADP-ribose) (PAR) to facilitate repair. There are limited biochemical and structural insights into the funct...

Radiation track and DNA damage

Recruitment of TRF2 to laser-induced DNA damage sites.

Several lines of evidence suggest that the telomere-associated protein TRF2 plays critical roles in the DNA damage response. TRF2 is rapidly and transiently phosphorylated by an ATM-dependent pathway in response to DNA damage and this DNA damage-induced phosphoryation is essential for the DNA-PK-dependent pathway of DNA double-strand break repair (DSB). However, the type of DNA damage that indu...

ATR kinase activation in G1 phase facilitates the repair of ionizing radiation-induced DNA damage

The kinase ATR is activated by RPA-coated single-stranded DNA generated at aberrant replicative structures and resected double strand breaks. While many hundred candidate ATR substrates have been identified, the essential role of ATR in the replicative stress response has impeded the study of ATR kinase-dependent signalling. Using recently developed selective drugs, we show that ATR inhibition ...

Uranium-Induced DNA Damage

The goal of this project is to see if and how uranium (U) may contribute to DNA damage. Radioactive forms of uranium have been used as fuel for nuclear reactors and as fissionable material for atomic weapons, tank armor, and ammunition shells. People who work with or live near processed uranium have experienced higher incidence of lung cancer, which has been attributed to radon, a radioactive d...