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Dale Andrew Ramsden

Professor

Research: Chromosome breaks, DNA repair, enzymes that repair DNA, Targeting DNA repair for cancer therapy, RNA in the chromosome.

Professor
(PhD – University of Toronto)

ACCEPTING STUDENTS

Trained Faculty Mentor endorsed by Office of Graduate Ed UNC Chapel Hill

HONORS & AWARDS

  • Leukemia and Lymphoma Society Scholarship: 2006-2011
  • Jefferson Pilot Fellowship: 2003-2006
  • Searle Scholar: 1999-2002
  • Cancer Research Institute Fellowship: 1996-1998
  • Governor General’s Gold Medal: 1994

Ramsden lab were the first to link several newly described DNA polymerases to NHEJ, and then showed how three different DNA polymerases make unique contributions to this pathway. They have varying substrate requirements that dictated their biological roles, and additionally have varying affinity for the NHEJ holoenzyme, ensuring a hierarchy of recruitment. His lab has additionally collaborated with several other groups in the research triangle area (Drs Kunkel, Pederson, and London, NIEHS; Dr. Lee, UNC) to clarify the structural basis for these differing biochemical characteristics.

Ramsden lab determined another component of NHEJ, Ku, has several unanticipated functions. His lab first determined it is sufficient for a kind of ?passive? chromatin remodeling: it peels DNA off the surface of nucleosomes without the typical requirement for ATP hydrolysis. More recently we characterized Ku as an enzyme. It is an AP lyase, and helps process damaged ends expected in the course of chromosome break repair. It is surprisingly one of the primary sources of AP lyase activity in cell extracts, and is uniquely active on its expected biological substrate (double strand breaks).

RESEARCH SUMMARY

Mammals use three distinct pathways for repairing chromosome breaks. Ramsden lab is interested in the mechanistic details of how each pathway works, but also how and why a given pathway is chosen, and the consequences of choosing the “wrong” pathway. Ramsden lab’s work has relevance to normal organismal development and aging, as well as carcinogenesis and cancer therapy. Notably, repair of chromosome breaks is also central to genome engineering.

Ramsden lab uses diverse approaches, including biochemical analyses and somatic cell genetics. Ramsden lab also work closely with a wide variety of labs with expertise in protein structure determination, biophysics, cell biology, and model organism genetics.

SELECTED PUBLICATIONS

  • Wyatt DW, Feng W, Conlin MP, Yousefzadeh MJ, Roberts SA, Mieczkowski P, Wood RD, Gupta GP, Ramsden DA. Essential roles for Polymerase θ mediated end-joining in repair of chromosome breaks. Mol Cell. 2016 Aug 18;63(4):662-73. *Featured paper.
  • Pryor JM*, Waters CA*, Aza A, Asagoshi K, Strom C, Mieczkowski PA, Blanco L, Ramsden DA. Essential role for polymerase specialization in cellular nonhomologous end joining. Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):E4537-45.
  • Waters CA, Strande NT, Pryor JM, Strom CN, Mieczkowski P, Burkhalter MD, Oh S, Qaqish BF, Moore DT, Hendrickson EA, Ramsden DA. The fidelity of the ligation step determines how ends are resolved during nonhomologous end joining. Nat Commun. 2014 Jul 3;5:4286.
  • Yousefzadeh MJ, Wyatt DW, Takata K, Mu Y, Hensley SC, Tomida J, Bylund GO, Doublié S, Johansson E, Ramsden DA, McBride KM, Wood RD. Mechanism of suppression of chromosomal instability by DNA polymerase POLQ. PLoS Genet. 2014 Oct;10(10):e1004654.
  • Roberts SA, Strande N, Burkhalter MD, Strom C, Havener JM, Hasty P, Ramsden DA. Ku is a 5′-dRP/AP lyase that excises nucleotide damage near broken ends. Nature. 2010 Apr 22;464(7292):1214-7.

Link to all pubs

  • Biochemistry & Biophysics