The Srs2 helicase dampens DNA damage checkpoint by recycling RPA from chromatin
Nalini Dhingra, Sahiti Kuppa, Lei Wei, Nilisha Pokhrel, Silva Baburyan, Xiang‐Zhou Meng, Edwin Antony, Xiaolan Zhao
Abstract
Significance In this work, we elucidate a checkpoint dampening mechanism in yeast. Using complementary biochemical and genetic approaches, we show that the Srs2 DNA helicase removes one of the first DNA damage sensors and the associated checkpoint kinase from chromatin, thus preventing hyperactivation of the DNA damage response. We further show that this role of Srs2 is separable from its well-known function as an antirecombinase and mainly accounts for Srs2’s contribution to genotoxin resistance. Our findings also shed light into potential means to regulate the dynamic association of RPA with single-stranded DNA in other cellular contexts and stimulate studies of checkpoint dampening and RPA regulation in other organisms.