상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

Break-induced ATR and Ddb1-Cul4Cdt2 ubiquitin ligase-dependent nucleotide synthesis promotes homologous recombination repair in fission yeast

Authors 

J MossH Tinline-PurvisC A WalkerL K FolkesM R StratfordJ HaylesKwang Lae HoeDong Uk KimH O ParkS E KearseyO FleckC HolmbergO NielsenT C Humphrey

Publisher 

Cold Spring Harbor Laboratory Press

Issue Date 

2010

Citation 

Genes & Development, vol. 24, no. 23, pp. 2705-2716

Keywords 

Ddb1-Cul4Cdt2 ubiquitin ligaseFission yeastHomologous recombination repairRad3Ribonucleotide reductaseSpd1

Abstract 

Nucleotide synthesis is a universal response to DNA damage, but how this response facilitates DNA repair and cell survival is unclear. Here we establish a role for DNA damage-induced nucleotide synthesis in homologous recombination (HR) repair in fission yeast. Using a genetic screen, we found the Ddb1-Cul4Cdt2 ubiquitin ligase complex and ribonucleotide reductase (RNR) to be required for HR repair of a DNA double-strand break (DSB). The Ddb1-Cul4Cdt2 ubiquitin ligase complex is required for degradation of Spd1, an inhibitor of RNR in fission yeast. Accordingly, deleting spd1 + suppressed the DNA damage sensitivity and the reduced HR efficiency associated with loss of ddb1+ or cdt2+. Furthermore, we demonstrate a role for nucleotide synthesis in postsynaptic gap filling of resected ssDNA ends during HR repair. Finally, we define a role for Rad3 (ATR) in nucleotide synthesis and HR through increasing Cdt2 nuclear levels in response to DNA damage. Our findings support a model in which break-induced Rad3 and Ddb1-Cul4Cdt2 ubiquitin ligase-dependent Spd1 degradation and RNR activation promotes postsynaptic ssDNA gap filling during HR repair. ? 2010 by Cold Spring Harbor Laboratory Press.

ISSN 

0890-9369

Link 

http://dx.doi.org/10.1101/gad.1970810

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


There are no files associated with this item.
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)