Quantitative sensing and signalling of single-stranded DNA during the DNA damage response.

ABSTRACT: The DNA damage checkpoint senses the presence of DNA lesions and controls the cellular response thereto. A crucial DNA damage signal is single-stranded DNA (ssDNA), which is frequently found at sites of DNA damage and recruits the sensor checkpoint kinase Mec1-Ddc2. However, how this signal - and therefore the cell's DNA damage load - is quantified, is poorly understood. Here, we use genetic manipulation of DNA end resection to induce quantitatively different ssDNA signals at a site-specific double strand break in budding yeast and identify two distinct signalling circuits within the checkpoint. The local checkpoint signalling circuit leading to γH2A phosphorylation is unresponsive to increased amounts of ssDNA, while the global checkpoint signalling circuit, which triggers Rad53 activatio

SUBMITTER: Bantele SCS 

PROVIDER: S-EPMC6391461 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature