PT  - JOURNAL ARTICLE
AU  - M. Woods
AU  - C.P. Barnes
TI  - Alternative end joining mechanisms exhibit varying dynamics in double strand break repair
AID  - 10.1101/026070
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 026070
4099  - http://biorxiv.org/content/early/2016/01/05/026070.short
4100  - http://biorxiv.org/content/early/2016/01/05/026070.full
AB  - Double strand breaks (DBSs) promote multiple repair pathways and can give rise to different mutagenic processes. The propensity for activation directly affects genomic instability, with implications across health and evolution. However, the relative contribution of these mechanisms, their interplay and regulatory interactions remain to be fully elucidated. Here we present a new method to model the combined activation of non-homologous end joining, single strand annealing and alternative end joining. We use Bayesian statistics to integrate eight biological data sets of DSB repair curves under varying genetic knockouts. 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 datasets are combined, the rate for intermediate repair is not constant amongst genetic knockouts. Further analysis suggests that the ratio between slow and intermediate repair depends on the presence or absence of DNAPKcs and Ku70. 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.