Periodic Reporting for period 1 - DNAcheck (Mechanistic analysis of DNA damage signaling and bypass upon replication of damaged DNA template in human cells.)
Okres sprawozdawczy: 2018-10-01 do 2020-09-30
While it is well known that the accumulation of single-stranded DNA (ssDNA) is the signal that riggers the checkpoint response, it is less clear how and where ssDNA actually arises. Generally, it is assumed to accumulate at stalled replication forks by an uncoupling between replicative helicase and polymerase movement. However, recent evidence found in budding yeast support a model where, in response to polymerase-blocking lesions, replication forks do not stall but recover efficiently by re-priming downstream of the lesions, thus leaving ssDNA gaps behind the fork. It is currently unknown whether this model also applies to vertebrate cells. Hence, this project aimed to address the fundamental question of how DNA damage is sensed during genome replication in human cells.
The results of the project have been presented to the scientific community at multiple conferences and workshops and are expected to be published within a year.