About

Steven J. Brill is a Professor at the Center for Advanced Biotechnology and Medicine at Rutgers University. His research interests include DNA replication, recombination, yeast genetics, DNA helicase, aging, and genome stability. He is involved in advancing understanding in these areas through his academic work at Rutgers, contributing to the fields of molecular biology and biochemistry.

Research topics

• Computer Science
• Genetics
• Biology
• World Wide Web

Selected publications

• GENETICS 2023 Reviewer Index

  Genetics. · 2023

  • Computer Science
  • Biology
  • Genetics

  to communicate significant research.To succeed, we must recognize what is significant, making sure the presentation is accurate, unambiguous, and easily readable.

  DOI

• Slx5-Slx8 ubiquitin ligase targets active pools of the Yen1 nuclease to limit crossover formation

  Nature Communications · 2018-11-21 · 22 citations

  articleOpen access

  The repair of double-stranded DNA breaks (DSBs) by homologous recombination involves the formation of branched intermediates that can lead to crossovers following nucleolytic resolution. The nucleases Mus81-Mms4 and Yen1 are tightly controlled during the cell cycle to limit the extent of crossover formation and preserve genome integrity. Here we show that Yen1 is further regulated by sumoylation and ubiquitination. In vivo, Yen1 becomes sumoylated under conditions of DNA damage by the redundant activities of Siz1 and Siz2 SUMO ligases. Yen1 is also a substrate of the Slx5-Slx8 ubiquitin ligase. Loss of Slx5-Slx8 stabilizes the sumoylated fraction, attenuates Yen1 degradation at the G1/S transition, and results in persistent localization of Yen1 in nuclear foci. Slx5-Slx8-dependent ubiquitination of Yen1 occurs mainly at K714 and mutation of this lysine increases crossover formation during DSB repair and suppresses chromosome segregation defects in a mus81∆ background.

  PublisherOA PDFDOI

• A Lysine Desert Protects a Novel Domain in the Slx5-Slx8 SUMO Targeted Ub Ligase To Maintain Sumoylation Levels in<i>Saccharomyces cerevisiae</i>

  Genetics · 2017-05-27 · 16 citations

  articleOpen accessSenior authorCorresponding

  Abstract Sumoylation is required to repair protein-linked DNA damage, but its presence can limit the use of alternative repair pathways. Through a suppressor... Protein modification by the small ubiquitin-like modifier (SUMO) plays important roles in genome maintenance. In Saccharomyces cerevisiae, proper regulation of sumoylation is known to be essential for viability in certain DNA repair mutants. Here, we find the opposite result; proper regulation of sumoylation is lethal in certain DNA repair mutants. Yeast cells lacking the repair factors TDP1 and WSS1 are synthetically lethal due to their redundant roles in removing Top1-DNA covalent complexes (Top1ccs). A screen for suppressors of tdp1∆ wss1∆ synthetic lethality isolated mutations in genes known to control global sumoylation levels including ULP1, ULP2, SIZ2, and SLX5. The results suggest that alternative pathways of repair become available when sumoylation levels are altered. Curiously, both suppressor mutations that were isolated in the Slx5 subunit of the SUMO-targeted Ub ligase created new lysine residues. These “slx5-K” mutations localize to a 398 amino acid domain that is completely free of lysine, and they result in the auto-ubiquitination and partial proteolysis of Slx5. The decrease in Slx5-K protein leads to the accumulation of high molecular weight SUMO conjugates, and the residual Ub ligase activity is needed to suppress inviability presumably by targeting polysumoylated Top1ccs. This “lysine desert” is found in the subset of large fungal Slx5 proteins, but not its smaller orthologs such as RNF4. The lysine desert solves a problem that Ub ligases encounter when evolving novel functional domains.

  PublisherOA PDFDOI

• Srs2 promotes Mus81–Mms4-mediated resolution of recombination intermediates

  Nucleic Acids Research · 2015-03-12 · 32 citations

  articleOpen access

  A variety of DNA lesions, secondary DNA structures or topological stress within the DNA template may lead to stalling of the replication fork. Recovery of such forks is essential for the maintenance of genomic stability. The structure-specific endonuclease Mus81-Mms4 has been implicated in processing DNA intermediates that arise from collapsed forks and homologous recombination. According to previous genetic studies, the Srs2 helicase may play a role in the repair of double-strand breaks and ssDNA gaps together with Mus81-Mms4. In this study, we show that the Srs2 and Mus81-Mms4 proteins physically interact in vitro and in vivo and we map the interaction domains within the Srs2 and Mus81 proteins. Further, we show that Srs2 plays a dual role in the stimulation of the Mus81-Mms4 nuclease activity on a variety of DNA substrates. First, Srs2 directly stimulates Mus81-Mms4 nuclease activity independent of its helicase activity. Second, Srs2 removes Rad51 from DNA to allow access of Mus81-Mms4 to cleave DNA. Concomitantly, Mus81-Mms4 inhibits the helicase activity of Srs2. Taken together, our data point to a coordinated role of Mus81-Mms4 and Srs2 in processing of recombination as well as replication intermediates.

  PublisherOA PDFDOI

• Multimerization domains are associated with apparent strand exchange activity in BLM and WRN DNA helicases

  DNA repair · 2014-09-03 · 6 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• Linking the Enzymes that Unlink DNA

  Molecular Cell · 2013-10-01 · 2 citations

  letterOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Bungling the easy stuff. Hospitals are still overcharging the poor. Obamacare was supposed to fix that too. What went wrong?

  PubMed · 2013-12-16 · 1 citations

  article1st authorCorresponding
  Publisher

• Resolution by Unassisted Top3 Points to Template Switch Recombination Intermediates during DNA Replication

  Journal of Biological Chemistry · 2013-10-08 · 8 citations

  articleOpen access

  The evolutionarily conserved Sgs1/Top3/Rmi1 (STR) complex plays vital roles in DNA replication and repair. One crucial activity of the complex is dissolution of toxic X-shaped recombination intermediates that accumulate during replication of damaged DNA. However, despite several years of study the nature of these X-shaped molecules remains debated. Here we use genetic approaches and two-dimensional gel electrophoresis of genomic DNA to show that Top3, unassisted by Sgs1 and Rmi1, has modest capacities to provide resistance to MMS and to resolve recombination-dependent X-shaped molecules. The X-shaped molecules have structural properties consistent with hemicatenane-related template switch recombination intermediates (Rec-Xs) but not Holliday junction (HJ) intermediates. Consistent with these findings, we demonstrate that purified Top3 can resolve a synthetic Rec-X but not a synthetic double HJ in vitro. We also find that unassisted Top3 does not affect crossing over during double strand break repair, which is known to involve double HJ intermediates, confirming that unassisted Top3 activities are restricted to substrates that are distinct from HJs. These data help illuminate the nature of the X-shaped molecules that accumulate during replication of damaged DNA templates, and also clarify the roles played by Top3 and the STR complex as a whole during the resolution of replication-associated recombination intermediates.

  PublisherOA PDFDOI

• RPA facilitates telomerase activity at chromosome ends in budding and fission yeasts

  The EMBO Journal · 2012-02-21 · 58 citations

  articleOpen access
  PublisherOA PDFDOI

• Epistasis analysis between homologous recombination genes in Saccharomyces cerevisiae identifies multiple repair pathways for Sgs1, Mus81-Mms4 and RNase H2

  Mutation research. Fundamental and molecular mechanisms of mutagenesis · 2011-07-05 · 17 citations

  articleSenior author
  PublisherDOI

Recent grants

• NIH Grant R01GM071268

  NIH · $2.5M · 2014

• NIH Grant R01GM067956

  NIH · $1.1M · 2008

• Mechanism of the BLM/Sgs1 Helicase Complex

  NIH · $1.3M · 2012–2018

• NIH Grant R01AG016637

  NIH · $1.3M · 2004

• NIH Grant R01GM055583

  NIH · $1.9M · 2007

Frequent coauthors

• Janet R. Mullen

  Rutgers, The State University of New Jersey

  14 shared

• William M. Fricke

  Rutgers, The State University of New Jersey

  6 shared

• Vivek Kaliraman

  6 shared

• Suzanne A. Bastin-Shanower

  Rutgers, The State University of New Jersey

  6 shared

• Miki Ii

  University of Alaska Anchorage

  5 shared

• M. John Chapman

  Massachusetts General Hospital

  4 shared

• Michael M. Gottesman

  National Cancer Institute

  4 shared

• Shu‐Chun Teng

  National Taiwan University

  4 shared

Education

• Ph.D., Molecular Biology and Biochemistry

  Rutgers, The State University of New Jersey