DNA Damage and Repair in Rodent and Human Cells after Exposure to JANUS Fission Spectrum Neutrons: A Minor Fraction of Single-strand Breaks as Revealed by Alkaline Elution is Refractory to Repair

1989 ◽  
Vol 55 (5) ◽  
pp. 761-772 ◽  
Author(s):  
M.J. Peak ◽  
J.G. Peak ◽  
B.A. Carnes ◽  
C.M. Chang Liu ◽  
C.K. Hill
1985 ◽  
Vol 226 (1) ◽  
pp. 175-182 ◽  
Author(s):  
I A G Roos ◽  
L P G Wakelin ◽  
S J Henry

The intracellular DNA damage produced by a series of diacridines after a 2 h pulse treatment of L1210 cells in culture was investigated by using the alkaline-elution technique. Like other intercalating agents, diacridines produce single-strand breaks and protein-DNA links. There is a large increase in both types of damage as the alkane chain linking the two 9-aminoacridine residues is increased beyond five methylene groups, which is consistent with the previously observed change from monofunctional to bifunctional intercalation [Wakelin, Romanos, Chen, Glaubiger, Canellakis & Waring (1978) Biochemistry 17, 5057-5063]. For linker chains of less than six methylene groups these agents produce less DNA damage than does the parent 9-aminoacridine at the same drug concentration. Unlike the monofunctional intercalators previously investigated [Ross, Glaubiger & Kohn (1979) Biochim. Biophys. Acta 562, 41-50; Zwelling, Michaels, Erickson, Ungerleider, Nichols & Kohn (1981) Biochemistry 20, 6553-6563; Zwelling, Kerrigan & Michaels (1982) Cancer Res. 42, 2687-2691; Zwelling, Michaels, Kerrigan, Pommier & Kohn (1982) Biochem. Pharmacol. 31, 3261-3267], there is no correlation between the number of single-strand breaks and protein-DNA links produced by these diacridines.


2018 ◽  
Vol 19 (8) ◽  
pp. 2389 ◽  
Author(s):  
Md. Hossain ◽  
Yunfeng Lin ◽  
Shan Yan

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.


2012 ◽  
Vol 19 (11) ◽  
pp. 1741-1749 ◽  
Author(s):  
P Fortini ◽  
C Ferretti ◽  
B Pascucci ◽  
L Narciso ◽  
D Pajalunga ◽  
...  

2000 ◽  
Vol 20 (4) ◽  
pp. 1206-1218 ◽  
Author(s):  
Jonathan G. Moggs ◽  
Paola Grandi ◽  
Jean-Pierre Quivy ◽  
Zophonías O. Jónsson ◽  
Ulrich Hübscher ◽  
...  

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.


Author(s):  
Piero Sestili ◽  
Marco Paolillo ◽  
Monia Lenzi ◽  
Evelin Colombo ◽  
Luciana Vallorani ◽  
...  

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