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.

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 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

Methylated DNA Causes a Physical Block to Replication Forks Independently of Damage Signalling, O6-Methylguanine or DNA Single-Strand Breaks and Results in DNA Damage

2010 ◽  
Vol 402 (1) ◽  
pp. 70-82 ◽  
Author(s):  
Petra Groth ◽  
Simon Ausländer ◽  
Muntasir Mamun Majumder ◽  
Niklas Schultz ◽  
Fredrik Johansson ◽  
...  
Keyword(s):  
Dna Damage ◽  
Single Strand ◽  
Replication Forks ◽  
Strand Breaks ◽  
Methylated Dna ◽  
Single Strand Breaks

scholarly journals Sensitivity of fresh acute myeloid leukemia cells to etoposide: relationship with cell growth characteristics and DNA single-strand breaks

Blood ◽  
1992 ◽  
Vol 80 (5) ◽  
pp. 1307-1315
Author(s):  
M Chiron ◽  
C Demur ◽  
V Pierson ◽  
JP Jaffrezou ◽  
C Muller ◽  
...  
Keyword(s):  
Dna Repair ◽  
Acute Myeloid Leukemia ◽  
Cell Growth ◽  
Cell Population ◽  
Myeloid Leukemia ◽  
Growth Characteristics ◽  
Single Strand ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Acute Myeloid

In this study, we evaluated the individual in vitro sensitivity of fresh acute myeloid leukemia (AML) cells to VP-16, and attempted to correlate VP-16 cytotoxicity with AML cell growth characteristics and drug-induced DNA single-strand breaks (SSB). Primary (PE1) colony inhibition assays allowed us to characterize two distinct groups of AML: group I (patients 1 through 6), which displayed sensitivity to VP- 16 similar to that of normal CFU-GM (IC90 of 20.52 +/- 2.44 micrograms/mL v 20.48 +/- 2.23 micrograms/mL after 1 hour drug exposure, respectively); and group II (patients 7 through 11), which was more sensitive to VP-16 (IC90 of 7.26 +/- 2.93 micrograms/mL, P = .004). Subsequently, groups I and II were termed normosensitive and hypersensitive, respectively. This objective VP-16 sensitivity classification, as determined by PE1, remained unaltered when assessed by secondary (PE2) colony inhibition assay (evaluating the self-renewal fraction of AML progenitors), or by cytofluorometric viability assay (evaluating the ultimately differentiated blast cell population). These findings would suggest that individual sensitivity to VP-16 of a particular cell population is maintained throughout CFU-AML differentiation. Finally, we report that sensitivity of AML cells to VP- 16 did not correlate either with cell growth characteristics or with SSB generation. Indeed, AML cell sensitivity to VP-16 appeared more closely related to DNA repair kinetics after drug removal, ie, hypersensitivity being essentially characterized by a prolonged retention of SSB during the posttreatment period. Interestingly, the established HL-60 cell line, which presented greater sensitivity to VP- 16 cytotoxicity than KG1, HEL, and K562, was also found to exhibit delayed DNA SSB repair kinetics, as compared with the other AML cell lines. These results suggest that hypersensitivity to VP-16 of some AML cells may be related to a deficient DNA-repair mechanism.

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