scholarly journals APE1 senses DNA single-strand breaks for repair and signaling

2019 ◽  
Vol 48 (4) ◽  
pp. 1925-1940 ◽  
Author(s):  
Yunfeng Lin ◽  
Jude Raj ◽  
Jia Li ◽  
Anh Ha ◽  
Md Akram Hossain ◽  
...  
Keyword(s):  
Dna Damage ◽  
Signaling Pathways ◽  
Somatic Tissue ◽  
Single Strand ◽  
Exonuclease Activity ◽  
Cancer Etiology ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
End Resection

Abstract DNA single-strand breaks (SSBs) represent the most abundant type of DNA damage. Unrepaired SSBs impair DNA replication and transcription, leading to cancer and neurodegenerative disorders. Although PARP1 and XRCC1 are implicated in the SSB repair pathway, it remains unclear how SSB repair and SSB signaling pathways are coordinated and regulated. Using Xenopus egg extract and in vitro reconstitution systems, here we show that SSBs are first sensed by APE1 to initiate 3′–5′ SSB end resection, followed by APE2 recruitment to continue SSB end resection. Notably, APE1’s exonuclease activity is critical for SSB repair and SSB signaling pathways. An APE1 exonuclease-deficient mutant identified in somatic tissue from a cancer patient highlighted the significance of APE1 exonuclease activity in cancer etiology. In addition, APE1 interacts with APE2 and PCNA, although PCNA is dispensable for APE1’s exonuclease activity. Taken together, we propose a two-step APE1/APE2-mediated mechanism for SSB end resection that couples DNA damage response with SSB repair in a eukaryotic system.

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 DNA damage response by single-strand breaks in terminally differentiated muscle cells and the control of muscle integrity

2012 ◽  
Vol 19 (11) ◽  
pp. 1741-1749 ◽  
Author(s):  
P Fortini ◽  
C Ferretti ◽  
B Pascucci ◽  
L Narciso ◽  
D Pajalunga ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Muscle Cells ◽  
Single Strand ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Damage Response

The Equine Estrogen Metabolite 4-Hydroxyequilenin Causes DNA Single-Strand Breaks and Oxidation of DNA Bases in Vitro

1998 ◽  
Vol 11 (9) ◽  
pp. 1105-1111 ◽  
Author(s):  
Yumei Chen ◽  
Li Shen ◽  
Fagen Zhang ◽  
Serrine S. Lau ◽  
Richard B. van Breemen ◽  
...  
Keyword(s):  
Single Strand ◽  
Dna Bases ◽  
Strand Breaks ◽  
Estrogen Metabolite ◽  
Oxidation Of Dna ◽  
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.

Chromosomal aberrations and deoxyribonucleic acid single-strand breaks in adipose-derived stem cells during long-term expansion in vitro

Cytotherapy ◽  
2013 ◽  
Vol 15 (7) ◽  
pp. 767-781 ◽  
Author(s):  
Katrin Froelich ◽  
Johannes Mickler ◽  
Gudrun Steusloff ◽  
Antje Technau ◽  
Mario Ramos Tirado ◽  
...  
Keyword(s):  
Stem Cells ◽  
Chromosomal Aberrations ◽  
Deoxyribonucleic Acid ◽  
Single Strand ◽  
Adipose Derived Stem Cells ◽  
Strand Breaks ◽  
Single Strand Breaks
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