scholarly journals Physical and Functional Interaction between DNA Ligase IIIα and Poly(ADP-Ribose) Polymerase 1 in DNA Single-Strand Break Repair

2003 ◽  
Vol 23 (16) ◽  
pp. 5919-5927 ◽  
Author(s):  
John B. Leppard ◽  
Zhiwan Dong ◽  
Zachary B. Mackey ◽  
Alan E. Tomkinson
Keyword(s):  
Dna Repair ◽  
Zinc Finger ◽  
Strand Break ◽  
Single Strand ◽  
Dna Ligase ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Parp 1 ◽  
Dna Ligase Iii

ABSTRACT The repair of DNA single-strand breaks in mammalian cells is mediated by poly(ADP-ribose) polymerase 1 (PARP-1), DNA ligase IIIα, and XRCC1. Since these proteins are not found in lower eukaryotes, this DNA repair pathway plays a unique role in maintaining genome stability in more complex organisms. XRCC1 not only forms a stable complex with DNA ligase IIIα but also interacts with several other DNA repair factors. Here we have used affinity chromatography to identify proteins that associate with DNA ligase III. PARP-1 binds directly to an N-terminal region of DNA ligase III immediately adjacent to its zinc finger. In further studies, we have shown that DNA ligase III also binds directly to poly(ADP-ribose) and preferentially associates with poly(ADP-ribosyl)ated PARP-1 in vitro and in vivo. Our biochemical studies have revealed that the zinc finger of DNA ligase III increases DNA joining in the presence of either poly(ADP-ribosyl)ated PARP-1 or poly(ADP-ribose). This provides a mechanism for the recruitment of the DNA ligase IIIα-XRCC1 complex to in vivo DNA single-strand breaks and suggests that the zinc finger of DNA ligase III enables this complex and associated repair factors to locate the strand break in the presence of the negatively charged poly(ADP-ribose) polymer.

scholarly journals The DNA-Binding Domain of Human PARP-1 Interacts with DNA Single-Strand Breaks as a Monomer through Its Second Zinc Finger

2011 ◽  
Vol 407 (1) ◽  
pp. 149-170 ◽  
Author(s):  
Sebastian Eustermann ◽  
Hortense Videler ◽  
Ji-Chun Yang ◽  
Paul T. Cole ◽  
Dominika Gruszka ◽  
...  
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Binding Domain ◽  
Single Strand ◽  
Dna Binding Domain ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Parp 1

scholarly journals Neuronal Enhancers are Hotspots For DNA Single-Strand Break Repair

2020 ◽  
Author(s):  
Wei Wu ◽  
Sarah E. Hill ◽  
William J. Nathan ◽  
Jacob Paiano ◽  
Kenta Shinoda ◽  
...  
Keyword(s):  
Dna Repair ◽  
Genome Stability ◽  
Cell Types ◽  
Strand Break ◽  
Single Strand ◽  
Single Strand Break ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Single Strand Break Repair ◽  
The Central Nervous System

Genome stability is essential for all cell types. However, defects in DNA repair frequently lead to neurodevelopmental and neurodegenerative diseases, underscoring the particular importance of DNA repair in long-lived post-mitotic neurons. The neuronal genome is subjected to a constant barrage of endogenous DNA damage due to high levels of oxidative metabolism in the central nervous system. Surprisingly, we know little about the identity of the lesion(s) that accumulate in neurons and whether they accrue throughout the genome or at specific loci. Here, we show that neurons, but not other post-mitotic cells, accumulate unexpectedly high numbers of DNA single-strand breaks (SSBs) at specific sites within the genome. These recurrent SSBs are found within enhancers, and trigger DNA repair through recruitment and activation of poly(ADP-ribose) polymerase-1 (PARP1) and XRCC1, the central SSB repair scaffold protein. Notably, deficiencies in PARP1, XRCC1, or DNA polymerase β elevate the localized incorporation of nucleotides, suggesting that the ongoing DNA synthesis at neuronal enhancers involves both short-patch and long-patch SSB repair processes. These data reveal unexpected levels of localized and continuous DNA single-strand breakage in neurons, suggesting an explanation for the neurodegenerative phenotypes that occur in patients with defective SSB repair.

scholarly journals Single-Strand Break End Resection in Genome Integrity: Mechanism and Regulation by APE2

2018 ◽  
Vol 19 (8) ◽  
pp. 2389 ◽  
Author(s):  
Md. Hossain ◽  
Yunfeng Lin ◽  
Shan Yan
Keyword(s):  
Dna Damage ◽  
Genome Instability ◽  
Strand Break ◽  
Single Strand ◽  
Genome Integrity ◽  
Single Strand Break ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Damage Response ◽  
End Resection

DNA single-strand breaks (SSBs) occur more than 10,000 times per mammalian cell each day, representing the most common type of DNA damage. Unrepaired SSBs compromise DNA replication and transcription programs, leading to genome instability. Unrepaired SSBs are associated with diseases such as cancer and neurodegenerative disorders. Although canonical SSB repair pathway is activated to repair most SSBs, it remains unclear whether and how unrepaired SSBs are sensed and signaled. In this review, we propose a new concept of SSB end resection for genome integrity. We propose a four-step mechanism of SSB end resection: SSB end sensing and processing, as well as initiation, continuation, and termination of SSB end resection. We also compare different mechanisms of SSB end resection and DSB end resection in DNA repair and DNA damage response (DDR) pathways. We further discuss how SSB end resection contributes to SSB signaling and repair. We focus on the mechanism and regulation by APE2 in SSB end resection in genome integrity. Finally, we identify areas of future study that may help us gain further mechanistic insight into the process of SSB end resection. Overall, this review provides the first comprehensive perspective on SSB end resection in genome integrity.

scholarly journals Cytogenetic markers, DNA single-strand breaks, urinary metabolites, and DNA repair rates in styrene-exposed lamination workers.

2004 ◽  
Vol 112 (8) ◽  
pp. 867-871 ◽  
Author(s):  
Pavel Vodicka ◽  
Jarno Tuimala ◽  
Rudolf Stetina ◽  
Rajiv Kumar ◽  
Paola Manini ◽  
...  
Keyword(s):  
Dna Repair ◽  
Urinary Metabolites ◽  
Single Strand ◽  
Strand Breaks ◽  
Single Strand Breaks

scholarly journals A CAF-1–PCNA-Mediated Chromatin Assembly Pathway Triggered by Sensing DNA Damage

2000 ◽  
Vol 20 (4) ◽  
pp. 1206-1218 ◽  
Author(s):  
Jonathan G. Moggs ◽  
Paola Grandi ◽  
Jean-Pierre Quivy ◽  
Zophonías O. Jónsson ◽  
Ulrich Hübscher ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Single Strand ◽  
Chromatin Assembly ◽  
Checkpoint Control ◽  
Free System ◽  
Strand Breaks ◽  
Assembly Pathway ◽  
Single Strand Breaks ◽  
Damaged Dna

ABSTRACT Sensing DNA damage is crucial for the maintenance of genomic integrity and cell cycle progression. The participation of chromatin in these events is becoming of increasing interest. We show that the presence of single-strand breaks and gaps, formed either directly or during DNA damage processing, can trigger the propagation of nucleosomal arrays. This nucleosome assembly pathway involves the histone chaperone chromatin assembly factor 1 (CAF-1). The largest subunit (p150) of this factor interacts directly with proliferating cell nuclear antigen (PCNA), and critical regions for this interaction on both proteins have been mapped. To isolate proteins specifically recruited during DNA repair, damaged DNA linked to magnetic beads was used. The binding of both PCNA and CAF-1 to this damaged DNA was dependent on the number of DNA lesions and required ATP. Chromatin assembly linked to the repair of single-strand breaks was disrupted by depletion of PCNA from a cell-free system. This defect was rescued by complementation with recombinant PCNA, arguing for role of PCNA in mediating chromatin assembly linked to DNA repair. We discuss the importance of the PCNA–CAF-1 interaction in the context of DNA damage processing and checkpoint control.

Sign in / Sign up

Export Citation Format

Share Document