RT Journal Article
SR Electronic
T1 Dynamics of endogenous PARP1 and PARP2 during DNA damage revealed by live-cell single-molecule imaging
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.03.12.484081
DO 10.1101/2022.03.12.484081
A1 Jyothi Mahadevan
A1 Asmita Jha
A1 Johannes Rudolph
A1 Samuel Bowerman
A1 Domenic Narducci
A1 Anders S Hansen
A1 Karolin Luger
YR 2022
UL http://biorxiv.org/content/early/2022/03/12/2022.03.12.484081.abstract
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.