The 9-1-1 checkpoint clamp coordinates resection at DNA double strand breaks

Ngo, Greg H.P. and Lydall, David 2015. The 9-1-1 checkpoint clamp coordinates resection at DNA double strand breaks. Nucleic Acids Research 43 (10) , 5017–5032. 10.1093/nar/gkv409

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Abstract

DNA-end resection, the generation of single-stranded DNA at DNA double strand break (DSB) ends, is critical for controlling the many cellular responses to breaks. Here we show that the conserved DNA damage checkpoint sliding clamp (the 9-1-1 complex) plays two opposing roles coordinating DSB resection in budding yeast. We show that the major effect of 9-1-1 is to inhibit resection by promoting the recruitment of Rad953BP1 near DSBs. However, 9-1-1 also stimulates resection by Exo1- and Dna2-Sgs1-dependent nuclease/helicase activities, and this can be observed in the absence of Rad953BP1. Our new data resolve the controversy in the literature about the effect of the 9-1-1 complex on DSB resection. Interestingly, the inhibitory role of 9-1-1 on resection is not observed near uncapped telomeres because less Rad953BP1 is recruited near uncapped telomeres. Thus, 9-1-1 both stimulates and inhibits resection and the effects of 9-1-1 are modulated by different regions of the genome. Our experiments illustrate the central role of the 9-1-1 checkpoint sliding clamp in the DNA damage response network that coordinates the response to broken DNA ends. Our results have implications in all eukaryotic cells.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Publisher:	Oxford University Press
ISSN:	1362-4962
Date of First Compliant Deposit:	11 April 2023
Date of Acceptance:	16 April 2015
Last Modified:	17 May 2023 21:23
URI:	https://orca.cardiff.ac.uk/id/eprint/158377

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