SOS regulatory elements are essential for UPEC pathogenesis

B. Li, P. Smith, D.J. Horvath, Jr, F.E. Romesberg, S.S. Justice, Microb. Infect. (2010) 12:662-668.
pubpic2010liEpithelial cells are highly regarded as the first line of defense against microorganisms, but the mechanisms used to control bacterial diseases are poorly understood. A component of the DNA damage repair regulon, SulA, is essential for UPEC virulence in a mouse model for human urinary tract infection, suggesting that DNA damage is a key mediator in the primary control of pathogens within the epithelium. In this study, we examine the role of DNA damage repair regulators in the intracellular lifestyle of UPEC within superficial bladder epithelial cells.


Identification of pathways controlling DNA damage induced mutation in Saccharomyces cerevisiae

E.T. Lis, B.M. O’Neill, C. Gil-Lemaignere, J.K. Chin, F.E. Romesberg, DNA Repair (2008) 7:801-810.
pubpic2008lisTo further understand the mutagenic response to DNA damage, we screen a collection of 4848 haploid gene deletion strains of S. cerevisiae for decreased damage-induced mutation of the CAN1 gene, and we identify a pathway of induced mutation that involves a replicative polymerase and that is effectively inhibited by the RNR inhibitor, hydroxyurea.


Psy2 and Pph3 form a phosphatase complex required for Rad53 dephosphorylation and replication fork restart during recovery from DNA damage

B.M. O’Neill, S.J. Szyjka, E.T. Lis, A.O. Bailey, J.R. Yates III, O.M. Aparicio, F.E. Romesberg, Proc. Natl. Acad. Sci. USA (2007) 104:9290-9295.
pubpic2007oneillWe present genetic and biochemical evidence that the type 2A-like protein phosphatase Pph3 forms a complex with Psy2 (Pph3–Psy2) that binds and dephosphorylates activated Rad53 during treatment with, and recovery from, methylmethane sulfonate-mediated DNA damage. Our findings suggest that Rad53 regulates replication fork restart and initiation of late firing origins independently and that regulation of these processes is mediated by specific Rad53 phosphatases order of magnitude relative to mispairing.


Esc4/Rtt107 and the control of recombination during replication

J.K. Chin, V.I. Bashkirov, W.-D. Heyer, F.E. Romesberg, DNA Repair (2006) 5:618-628.
pubpic2006chinWe show that Esc4 interacts with several proteins involved in the repair and processing of stalled or collapsed replication forks, including the recombination protein Rad55, and we propose that Esc4 associates with ssDNA of stalled forks and acts as a scaffolding protein to recruit and/or modulate the function of other proteins required to reinitiate DNA synthesis.


Coordinated functions of WSS1, PSY2, and TOF1 in the DNA damage response

B.M. O’Neill, D. Hanway, E.A. Winzeler, F.E. Romesberg, Nucleic Acids Res. (2004) 32:6519–6530.
pubpic2004oneillThe stabilization and processing of stalled replication forks is required to maintain genome integrity in all organisms. Based on both physical and genetic interactions detected between WSS1, PSY2, and TOF1, we suggest that Wss1 and Psy2 similarly function to stabilize or process stalled or collapsed replication forks.