Imperial College London
Alternate

ProfessorLuisAragon Alcaide

Faculty of Medicine, Institute of Clinical Sciences

Professor of Genetics
 
 
 
//

Contact

 

+44 (0)20 3313 8013luis.aragon

 
 
//

Location

 

CRB (Clinical Research Building)Hammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Patel:2015,
author = {Patel, A and Aragon, L},
journal = {Blood},
pages = {2421--2421},
title = {A Double Strand Break during Telophase Is Repaired with Homologous Recombination Despite the Absence of an Available Sister Chromatid},
volume = {126},
year = {2015}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background:Chromosomal breakage results from a DNA double strand break (DSB), and is repaired to maintain and restore genetic integrity, principally through two major pathways: homologous recombination (HR) and non-homologous end-joining (NHEJ). HR is initiated by nucleolytic resection of a DSB in the presence of cyclin-dependent kinase 1 (Cdk1) activity. DSB repair through HR is dependent on Rad52, and can be error-free when a sister chromatid is used as a template for repair. However, HR is mutagenic when any other template is used for repair. Loss of nucleotides adjacent to the DSB is a feature of repair through NHEJ. There is co-relation between Cdk1 activity and the presence of a sister chromatid. The research question was, in addition to Cdk1 activity is the presence of an intact sister chromatid a requirement to initiate DSB repair with the HR pathway.Methods:Cdk1 activity peaks during mitosis in the presence of an intact sister chromatid. To study DSB resection and repair in cells arrested in either mitotic metaphase or telophase when Cdk1-Clb2 was active, conditional alleles were constructed in a eukaryotic haploid budding yeast model of HR. The model permitted simultaneous induction of a single site-specific DSB in cells that were synchronised to a phase of the cell division cycle. Physical monitoring of the kinetics of DSB formation, nucleolytic resection of adjacent DNA, and DSB repair, was achieved by probing Southern membranes after restriction enzyme digestion of extracted genomic DNA from time courses.Results:Sister chromatids were segregated during telophase arrest induced by either Cdc14 or Cdc15 depletion. Metaphase arrest was achieved with Cdc20 depletion, either directly, or indirectly by activation of the spindle assembly checkpoint by inhibition of microtubule polymerisation. Sister chromatids were unsegregated and physically attached through cohesin during metaphase.The absence of an intact sister chromatid did not prevent DSB repair with the
AU  - Patel,A
AU  - Aragon,L
EP  - 2421
PY  - 2015///
SN  - 0006-4971
SP  - 2421
TI  - A Double Strand Break during Telophase Is Repaired with Homologous Recombination Despite the Absence of an Available Sister Chromatid
T2  - Blood
VL  - 126
ER  -
Download