DNA replication forks pause in front of lesions on the template, eventually leading to cytotoxic chromosomal rearrangements. The in vivo structure of damaged eukaryotic replication intermediates has been so far elusive. Combining electron microscopy (EM) and two-dimensional (2D) gel electrophoresis, we found that UV-irradiated S. cerevisiae cells uncouple leading and lagging strand replication ...

Replication of Saccharomyces ribosomal DNA (rDNA) proceeds bidirectionally from origins in a subset of the approximately 150 tandem repeats, but the leftward-moving fork stops when it encounters the replication fork barrier (RFB). The Pif1p helicase and the highly related Rrm3p were rDNA associated in vivo. Both proteins affected rDNA replication but had opposing effects on fork progression. Pi...

The fork-join queue models parallel resources where arriving jobs divide into various number of sub-tasks that are assigned to unique devices within the parallel resource. Each device in the parallel resource is modeled by M=M=1 queueing servers. A job completes execution and departs the parallel resource after all its sub-tasks complete execution. This paper analyzes N-server fork-join queues ...

The yeast checkpoint factors Mrc1p and Tof1p travel with the replication fork and mediate the activation of the Rad53p kinase in response to a replication stress. We show here that both proteins are required for normal fork progression but play different roles at stalled forks. Tof1p is critical for the activity of the rDNA replication fork barrier (RFB) but plays a minor role in the replicatio...

Human cells must faithfully duplicate billions of base pairs of DNA every cell division cycle. Insufficient precursors, DNA damage, and difficult-to-replicate sequences cause replication fork stalling. Even in the best of circumstances, hundreds of forks may stall during each S phase in a human cell, and the frequency increases in cells exposed to genotoxic or oncogenic stresses. Cells must res...

Algebraization of computational logics in the theory of fork algebras has been a research topic for a while. This research allowed us to interpret classical first-order logic, several propositional monomodal logics, propositional and first-order dynamic logic, and propositional and first-order linear temporal logic in the theory of fork algebras. In this paper we formalize these interpretabilit...

Defective DNA repair causes Fanconi anemia (FA), a rare childhood cancer-predisposing syndrome. At least 15 genes are known to be mutated in FA; however, their role in DNA repair remains unclear. Here, we show that the FANCJ helicase promotes DNA replication in trans by counteracting fork stalling on replication barriers, such as G4 quadruplex structures. Accordingly, stabilization of G4 quadru...

Replication stress activates the Mec1(ATR) and Rad53 kinases. Rad53 phosphorylates nuclear pores to counteract gene gating, thus preventing aberrant transitions at forks approaching transcribed genes. Here, we show that Rrm3 and Pif1, DNA helicases assisting fork progression across pausing sites, are detrimental in rad53 mutants experiencing replication stress. Rrm3 and Pif1 ablations rescue ce...