PT  - JOURNAL ARTICLE
AU  - Jyothi Mahadevan
AU  - Asmita Jha
AU  - Johannes Rudolph
AU  - Samuel Bowerman
AU  - Domenic Narducci
AU  - Anders S Hansen
AU  - Karolin Luger
TI  - Dynamics of endogenous PARP1 and PARP2 during DNA damage revealed by live-cell single-molecule imaging
AID  - 10.1101/2022.03.12.484081
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.03.12.484081
4099  - http://biorxiv.org/content/early/2022/03/12/2022.03.12.484081.short
4100  - http://biorxiv.org/content/early/2022/03/12/2022.03.12.484081.full
AB  - PARP1 contributes to genome architecture and DNA damage repair through its dynamic association with chromatin. PARP1 and PARP2 (PARP1/2) recognize damaged DNA and recruit the DNA repair machinery. Using single molecule microscopy in live cells, we monitored the movement of PARP1/2 on undamaged and damaged chromatin. We identify two classes of freely diffusing PARP1/2 and two classes of bound PARP1/2. The majority (> 60%) of PARP1/2 diffuse freely in both undamaged and damaged nuclei and in the presence of inhibitors of PARP1/2 used for cancer therapy (PARPi). Laser induced DNA damage results in a small fraction of slowly diffusing PARP1 and PARP2 to become transiently bound. Treatment of cells with PARPi in the presence of DNA damage causes subtle changes in the dynamics of bound PARP1/2, in contrast to bulk studies that suggest PARP trapping. Our results imply that next-generation PARPi could specifically target the small fraction of DNA-bound PARP1/2.Competing Interest StatementThe authors have declared no competing interest.