Radiation-Induced Chromosomal Breaks may be DNA Repair Fragile Sites with Larger-scale Correlations to Eight Double-Strand-Break Related Data Sets over the Human Genome

2019 ◽  
Vol 192 (5) ◽  
pp. 562
Author(s):  
Anders Brahme ◽  
Maj Hultén ◽  
Carin Bengtsson ◽  
Andreas Hultgren ◽  
Anders Zetterberg
Keyword(s):  
Dna Repair ◽  
Human Genome ◽  
Strand Break ◽  
Double Strand Break ◽  
Fragile Sites ◽  
Data Sets ◽  
Related Data ◽  
Chromosomal Breaks ◽  
Radiation Induced

scholarly journals Mechanistic modelling and Bayesian inference elucidates the variable dynamics of double-strand break repair

2015 ◽  
Author(s):  
M. Woods ◽  
C.P. Barnes
Keyword(s):  
Dna Repair ◽  
Strand Break ◽  
Double Strand Break ◽  
Double Strand Breaks ◽  
Data Sets ◽  
End Joining ◽  
Strand Breaks ◽  
Alternative End Joining ◽  
Intermediate Repair ◽  
Non Homologous End Joining

AbstractDNA double-strand breaks are lesions that form during metabolism, DNA replication and exposure to mutagens. When a double-strand break occurs one of a number of repair mechanisms is recruited, all of which have differing propensities for mutational events. Despite DNA repair being of crucial importance, the relative contribution of these mechanisms and their regulatory interactions remain to be fully elucidated. Understanding these mutational processes will have a profound impact on our knowledge of genomic instability, with implications across health, disease and evolution. Here we present a new method to model the combined activation of non-homologous end joining, single strand annealing and alternative end joining, following exposure to ionizing radiation. We use Bayesian statistics to integrate eight biological data sets of double-strand break repair curves under varying genetic knockouts and confirm that our model is predictive by re-simulating and comparing to additional data. Analysis of the model suggests that there are at least three disjoint modes of repair, which we assign as fast, slow and intermediate. Our results show that when multiple data sets are combined, the rate for intermediate repair is variable amongst genetic knockouts. Further analysis suggests that the ratio between slow and intermediate repair depends on the presence or absence of DNA-PKcs and Ku70, which implies that non-homologous end joining and alternative end joining are not independent. Finally, we consider the proportion of double-strand breaks within each mechanism as a time series and predict activity as a function of repair rate. We outline how our insights can be directly tested using imaging and sequencing techniques and conclude that there is evidence of variable dynamics in alternative repair pathways. Our approach is an important step towards providing a unifying theoretical framework for the dynamics of DNA repair processes.

scholarly journals Nuclear phosphoinositide 3-kinase   controls double-strand break DNA repair

2010 ◽  
Vol 107 (16) ◽  
pp. 7491-7496 ◽  
Author(s):  
A. Kumar ◽  
O. Fernandez-Capetillo ◽  
A. C. Carrera
Keyword(s):  
Dna Repair ◽  
Strand Break ◽  
Double Strand Break ◽  
Phosphoinositide 3 Kinase

A Review of Studies of Ionizing Radiation-Induced Double-Strand Break Clustering

2001 ◽  
Vol 156 (5) ◽  
pp. 572-576 ◽  
Author(s):  
K. M. Prise ◽  
M. Pinto ◽  
H. C. Newman ◽  
B. D. Michael
Keyword(s):  
Ionizing Radiation ◽  
Strand Break ◽  
Double Strand Break ◽  
Radiation Induced

“Polymorphisms in double strand break repair related genes influence radiosensitivity phenotype in lymphocytes from healthy individuals” [DNA Repair 40 (2016) 27–34]

DNA Repair ◽  
2016 ◽  
Vol 43 ◽  
pp. 113
Author(s):  
Kamalesh Dattaram Mumbrekar ◽  
Hassan Venkatesh Goutham ◽  
Bejadi Manjunath Vadhiraja ◽  
Satish Rao Bola Sadashiva
Keyword(s):  
Dna Repair ◽  
Strand Break ◽  
Double Strand Break ◽  
Double Strand Break Repair ◽  
Healthy Individuals ◽  
Break Repair

scholarly journals Ubiquitylation-Mediated Fine-Tuning of DNA Double-Strand Break Repair

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1617
Author(s):  
Barbara N. Borsos ◽  
Hajnalka Majoros ◽  
Tibor Pankotai
Keyword(s):  
Dna Repair ◽  
Strand Break ◽  
Double Strand Break ◽  
Fine Tuning ◽  
Double Strand Break Repair ◽  
Proper Function ◽  
Dna Damages ◽  
Regulatory Pathways ◽  
Dna Double Strand Break ◽  
Break Repair

The proper function of DNA repair is indispensable for eukaryotic cells since accumulation of DNA damages leads to genome instability and is a major cause of oncogenesis. Ubiquitylation and deubiquitylation play a pivotal role in the precise regulation of DNA repair pathways by coordinating the recruitment and removal of repair proteins at the damaged site. Here, we summarize the most important post-translational modifications (PTMs) involved in DNA double-strand break repair. Although we highlight the most relevant PTMs, we focus principally on ubiquitylation-related processes since these are the most robust regulatory pathways among those of DNA repair.

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