Accumulation of p21 proteins at DNA damage sites independent of p53 and core NHEJ factors following irradiation

2011 ◽  
Vol 412 (1) ◽  
pp. 39-43 ◽  
Author(s):  
Manabu Koike ◽  
Yasutomo Yutoku ◽  
Aki Koike
Keyword(s):  
Dna Damage ◽  
P21 Proteins

Apoptotic resistance to ionizing radiation in pediatric B-precursor acute lymphoblastic leukemia frequently involves increased NF-κB survival pathway signaling

Blood ◽  
2004 ◽  
Vol 104 (5) ◽  
pp. 1465-1473 ◽  
Author(s):  
Victoria J. Weston ◽  
Belinda Austen ◽  
Wenbin Wei ◽  
Eliot Marston ◽  
Azra Alvi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Acute Lymphoblastic Leukemia ◽  
Ionizing Radiation ◽  
Lymphoblastic Leukemia ◽  
Response To Treatment ◽  
Variable Response ◽  
Caspase Cleavage ◽  
Survival Pathway ◽  
Resistance To Ionizing Radiation ◽  
P21 Proteins

Abstract To investigate possible causes of the variable response to treatment in pediatric B-precursor acute lymphoblastic leukemia (ALL) and to establish potential novel therapeutic targets, we used ionizing radiation (IR) exposure as a model of DNA damage formation to identify tumors with resistance to p53-dependent apoptosis. Twenty-one of 40 ALL tumors responded normally to IR, exhibiting accumulation of p53 and p21 proteins and cleavage of caspases 3, 7, and 9 and of PARP1. Nineteen tumors exhibited apoptotic resistance and lacked PARP1 and caspase cleavage; although 15 of these tumors had normal accumulation of p53 and p21 proteins, examples exhibited abnormal expression of TRAF5, TRAF6, and cIAP1 after IR, suggesting increased NF-κB prosurvival signaling as the mechanism of apoptotic resistance. The presence of a hyperactive PARP1 mutation in one tumor was consistent with such increased NF-κB activity. PARP1 inhibition restored p53-dependent apoptosis after IR in these leukemias by reducing NF-κB DNA binding and transcriptional activity. In the remaining 4 ALL tumors, apoptotic resistance was associated with a TP53 mutation or with defective activation of p53. We conclude that increased NF-κB prosurvival signaling is a frequent mechanism by which B-precursor ALL tumors develop apoptotic resistance to IR and that PARP1 inhibition may improve the DNA damage response of these leukemias.

1576: Prediction of Spermatozoal DNA Damage by a Novel Semen Quality Score

2004 ◽  
Vol 171 (4S) ◽  
pp. 416-416
Author(s):  
Tamer M. Said ◽  
Shyam Allamaneni ◽  
Kiran P. Nallella ◽  
Rakesh K. Sharma ◽  
Sijo J. Parekattil ◽  
...  
Keyword(s):  
Dna Damage ◽  
Semen Quality ◽  
Quality Score

A safe fix for alcohol-derived DNA damage

Nature ◽  
2020 ◽  
Vol 579 (7800) ◽  
pp. 499-500
Author(s):  
Irene Gallina ◽  
Julien P. Duxin
Keyword(s):  
Dna Damage

Use of the comet assay to measure DNA damage in cells exposed to photosensitizers and gamma radiation

1999 ◽  
Vol 96 (1) ◽  
pp. 143-146 ◽  
Author(s):  
J.-P. Pouget ◽  
J.-L. Ravanat ◽  
T. Douki ◽  
M.-J. Richard ◽  
J. Cadet
Keyword(s):  
Dna Damage ◽  
Comet Assay ◽  
Gamma Radiation ◽  
In Cells

Bestimmung der DNA-Schädigung in vitro

2010 ◽  
Vol 49 (S 01) ◽  
pp. S64-S68
Author(s):  
E. Dikomey
Keyword(s):  
Dna Damage ◽  
Cell Lines ◽  
Chromosome Aberrations ◽  
Genetic Factors ◽  
Double Strand Breaks ◽  
Strand Breaks ◽  
Cell Inactivation ◽  
Repair Mechanisms ◽  
Break Repair

SummaryIonising irradiation acts primarily via induction of DNA damage, among which doublestrand breaks are the most important lesions. These lesions may lead to lethal chromosome aberrations, which are the main reason for cell inactivation. Double-strand breaks can be repaired by several different mechanisms. The regulation of these mechanisms appears be fairly different for normal and tumour cells. Among different cell lines capacity of doublestrand break repair varies by only few percents and is known to be determined mostly by genetic factors. Knowledge about doublestrand break repair mechanisms and their regulation is important for the optimal application of ionising irradiation in medicine.

Sign in / Sign up

Export Citation Format

Share Document