ADP-Ribosylation, DNA Repair, and Chromatin Organization

1985 ◽  
pp. 235-241 ◽  
Author(s):  
Felix R. Althaus ◽  
Georg Mathis
Keyword(s):  
Dna Repair ◽  
Chromatin Organization ◽  
Adp Ribosylation

scholarly journals HPF1 remodels the active site of PARP1 to enable the serine ADP-ribosylation of histones

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Fa-Hui Sun ◽  
Peng Zhao ◽  
Nan Zhang ◽  
Lu-Lu Kong ◽  
Catherine C. L. Wong ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Active Site ◽  
Negative Charge ◽  
Structural Data ◽  
Dna Breaks ◽  
Adp Ribosylation ◽  
Local Conformation ◽  
Key Residues ◽  
Structural Insights

AbstractUpon binding to DNA breaks, poly(ADP-ribose) polymerase 1 (PARP1) ADP-ribosylates itself and other factors to initiate DNA repair. Serine is the major residue for ADP-ribosylation upon DNA damage, which strictly depends on HPF1. Here, we report the crystal structures of human HPF1/PARP1-CAT ΔHD complex at 1.98 Å resolution, and mouse and human HPF1 at 1.71 Å and 1.57 Å resolution, respectively. Our structures and mutagenesis data confirm that the structural insights obtained in a recent HPF1/PARP2 study by Suskiewicz et al. apply to PARP1. Moreover, we quantitatively characterize the key residues necessary for HPF1/PARP1 binding. Our data show that through salt-bridging to Glu284/Asp286, Arg239 positions Glu284 to catalyze serine ADP-ribosylation, maintains the local conformation of HPF1 to limit PARP1 automodification, and facilitates HPF1/PARP1 binding by neutralizing the negative charge of Glu284. These findings, along with the high-resolution structural data, may facilitate drug discovery targeting PARP1.

scholarly journals RAP80 and BRCA1 PARsylation protect chromosome integrity by preventing retention of BRCA1-B/C complexes in DNA repair foci

2020 ◽  
Vol 117 (4) ◽  
pp. 2084-2091
Author(s):  
Jekaterina Vohhodina ◽  
Kimberly J. Toomire ◽  
Sarah A. Petit ◽  
Goran Micevic ◽  
Geeta Kumari ◽  
...  
Keyword(s):  
Dna Repair ◽  
Homologous Recombination ◽  
Complex Formation ◽  
Illegitimate Recombination ◽  
Adp Ribosylation ◽  
Chromosomal Disorder ◽  
Nuclear Foci ◽  
Simultaneous Loss ◽  
Chromosome Integrity ◽  
Focal Structures

BRCA1 promotes error-free, homologous recombination-mediated repair (HRR) of DNA double-stranded breaks (DSBs). When excessive and uncontrolled, BRCA1 HRR activity promotes illegitimate recombination and genome disorder. We and others have observed that the BRCA1-associated protein RAP80 recruits BRCA1 to postdamage nuclear foci, and these chromatin structures then restrict the amplitude of BRCA1-driven HRR. What remains unclear is how this process is regulated. Here we report that both BRCA1 poly-ADP ribosylation (PARsylation) and the presence of BRCA1-bound RAP80 are critical for the normal interaction of BRCA1 with some of its partners (e.g., CtIP and BACH1) that are also known components of the aforementioned focal structures. Surprisingly, the simultaneous loss of RAP80 and failure therein of BRCA1 PARsylation results in the dysregulated accumulation in these foci of BRCA1 complexes. This in turn is associated with the intracellular development of a state of hyper-recombination and gross chromosomal disorder. Thus, physiological RAP80-BRCA1 complex formation and BRCA1 PARsylation contribute to the kinetics by which BRCA1 HRR-sustaining complexes normally concentrate in nuclear foci. These events likely contribute to aneuploidy suppression.

ADP-RIBOSYLATION AND DNA REPAIR AS INDUCED BY NITROSOUREAS

Nitrosoureas ◽  
1981 ◽  
pp. 123-142
Author(s):  
Mark Smulson ◽  
Tauseef Butt ◽  
Swaroop Sudhakar ◽  
Don Jump ◽  
Nancy Nolan
Keyword(s):  
Dna Repair ◽  
Adp Ribosylation

scholarly journals PARP1-Driven Poly-ADP-Ribosylation Regulates BRCA1 Function in Homologous Recombination–Mediated DNA Repair

2014 ◽  
Vol 4 (12) ◽  
pp. 1430-1447 ◽  
Author(s):  
Yiduo Hu ◽  
Sarah A. Petit ◽  
Scott B. Ficarro ◽  
Kimberly J. Toomire ◽  
Anyong Xie ◽  
...  
Keyword(s):  
Dna Repair ◽  
Homologous Recombination ◽  
Adp Ribosylation

scholarly journals Reversible ADP-ribosylation of RNA

2019 ◽  
Vol 47 (11) ◽  
pp. 5658-5669 ◽  
Author(s):  
Deeksha Munnur ◽  
Edward Bartlett ◽  
Petra Mikolčević ◽  
Ilsa T Kirby ◽  
Johannes Gregor Matthias Rack ◽  
...  
Keyword(s):  
Dna Repair ◽  
Stress Response ◽  
Nicotinamide Adenine Dinucleotide ◽  
Cellular Stress Response ◽  
Biological Processes ◽  
Adp Ribosylation ◽  
Human Proteins ◽  
Novel Target ◽  
Host Virus Interactions ◽  
Virus Interactions

Abstract ADP-ribosylation is a reversible chemical modification catalysed by ADP-ribosyltransferases such as PARPs that utilize nicotinamide adenine dinucleotide (NAD+) as a cofactor to transfer monomer or polymers of ADP-ribose nucleotide onto macromolecular targets such as proteins and DNA. ADP-ribosylation plays an important role in several biological processes such as DNA repair, transcription, chromatin remodelling, host-virus interactions, cellular stress response and many more. Using biochemical methods we identify RNA as a novel target of reversible mono-ADP-ribosylation. We demonstrate that the human PARPs - PARP10, PARP11 and PARP15 as well as a highly diverged PARP homologue TRPT1, ADP-ribosylate phosphorylated ends of RNA. We further reveal that ADP-ribosylation of RNA mediated by PARP10 and TRPT1 can be efficiently reversed by several cellular ADP-ribosylhydrolases (PARG, TARG1, MACROD1, MACROD2 and ARH3), as well as by MACROD-like hydrolases from VEEV and SARS viruses. Finally, we show that TRPT1 and MACROD homologues in bacteria possess activities equivalent to the human proteins. Our data suggest that RNA ADP-ribosylation may represent a widespread and physiologically relevant form of reversible ADP-ribosylation signalling.

scholarly journals Repairing split ends: SIRT6, mono-ADP ribosylation and DNA repair

Aging ◽  
2011 ◽  
Vol 3 (9) ◽  
pp. 829-835 ◽  
Author(s):  
Michael Van Meter ◽  
Zhiyong Mao ◽  
Vera Gorbunova ◽  
Andrei Seluanov
Keyword(s):  
Dna Repair ◽  
Adp Ribosylation ◽  
Split Ends
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