Contact Information
Yilun Liu, Ph.D.
  • Associate Chair and Associate Professor, Radiation Biology

Research

 
Research
 
Dr. Liu’s laboratory aims to understand how defects in DNA synthesis and repair contribute to cancer pathogenesis and aging. Specifically, her team focuses on a set of proteins belonging to the RECQ family of DNA helicases are among the cancer suppressors linked to DNA repair, replication and genome maintenance. During the course of evolution, RECQ genes appear to have been amplified and diverged from a single copy of the RecQ gene in bacteria and yeast to five RECQ homologs in humans. The human RECQ proteins share many similar biochemical properties in vitro, yet these proteins are not redundant, as mutations in different RECQ proteins lead to different clinical syndromes including premature aging. In addition, a defect in one RECQ protein is sufficient to cause cell transformation and tumorigenesis, and this defect cannot be compensated by other RECQ proteins. Dr. Liu’s long-term agenda in dissecting the functions of individual RECQ proteins in human cells and comparing the similarities and differences among the RECQ proteins is to understand what aspects of genome maintenance and DNA metabolism are required for normal development and cancer prevention.

Publications

 
Publications
 
Undergraduate, MIT (1991-1995)
McCreath KJ, Specht CA, Liu Y, Robbins PW (1996) Molecular Cloning of a Third Chitinase (CHT1) from Candida albicans. Yeast 12, 501-504.

Specht CA, Liu Y, Robbins PW, Bulawa CE, Iartchouk N, Winter KR, Riggle PJ, Rhodes JC, Dodge CL, Culp DW, Borgia PT (1996) The chsD and chsE genes of Aspergillus nidulans and their roles in chitin synthesis. Fungal Genetics and Biology 20, 153-167.
 
Xoconostle-Cazares B, Specht CA, Robbins PW, Liu Y, Leon C, Ruiz-Herrera J (1997) Umchs5, a gene coding for a class IV chitin synthase in Ustilago maydis. Fungal Genet and Biol  22, 199-208.
 
de la Vega-Hernandez H, Specht CA, Liu Y, Robbins PW (1998) Chitinases are a multi-gene family in Aedes, Anopheles and Drosophila. Insect Mol Biol 7, 233-239.
 
Ph.D., Yale University (1995-2000)
Liu Y, Li M-J, Lee EY, Maizels N (1999) Localization and dynamic relocalization of Mammalian Rad52 during the cell cycle and in response to DNA damage. Curr Biol 9, 975-978.

Liu Y, Maizels N (2000) Coordinated Response of Mammalian Rad51 and Rad52 to DNA damage. EMBO Rep 1, 85-90.

Postdoctoral Fellow, Cancer Research UK (2001-2006)
Liu Y, West SC (2002) Distinct functions of BRCA1 and BRCA2 in double-strand break repair. Breast Cancer Res 4, 9-13.

Singleton MR, Wentzell LM, Liu Y, West SC, Wigley DB (2002) Structure of the single-strand annealing domain of human RAD52 protein. Proc Natl Acad Sci U S A 99, 13492-13497.

Liu Y, Stasiak AZ, Masson J-Y, Stasiak A, West SC (2004) Conformational changes modulate the activity of human RAD51 protein. J Mol Biol 337, 817-827.

Garcia LP, Liu Y, Jiricny J, West SC, Janscak P (2004) Human RecQ5, a protein with DNA helicase and strand-annealing activities on the same polypeptide. EMBO J 23, 2882-2891.

Liu Y, Masson J-Y, Shah R, O’-Regan P, West SC (2004) RAD51C is required for Holliday Junction processing in mammalian cells. Science 303, 243-246.

Liu Y, West SC (2004) Happy Hollidays: 40th Anniversary of the Holliday Junction. Nature Rev in Mol Cell Biol 5, 937-944.
 
Esashi F, Chris N, Gannon J, Liu Y, Hunt T, Jasin M, West SC (2005) CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair. Nature 434, 598-604.
 
McIlwraith MJ, Vaisman A, Liu Y, Fanning E, Woodgate R, West SC (2005) Human DNA Polymerase  promotes DNA synthesis from strand invasion intermediates (D-loops) of homologous recombination. Mol Cell 20, 783-792.
 
Kuznetsov S, Pellegrini M, Shuda K,Fernandes-Capetillo O, Liu Y, Martin BK, Burkett S, Southon E, Pati D, Tessarollo L, West SC, Donavan PJ, Nussenzweig A, Sharan SK (2007) RAD51C deficiency in mice results in early prophase I arrest in males and sister chromatid separation at metaphase II in females. J Cell Biol 176, 581-592.

Liu Y, Tarsounas M, O’Regan P, West SC (2007) Role of RAD51C and XRCC3 in genetic recombination and DNA repair. J Biol Chem, 282, 1973-1979.

Assistant Professor, Yale University School of Medicine (2006-2011)
Aygun O, Svejstrup J, Liu Y (2008) A RECQ5-RNA Polymerase II association identified by targeted proteomic analysis of human chromatin. Proc Natl Acad Sci U S A 105, 8580-8584.

Liu Y, West SC (2008) More Complexity to the Bloom’s Syndrome Complex. Genes Dev 15, 2737-2742.
 
Xu X, Liu Y (2009) Dual DNA unwinding activities of the human Rothmund-Thomson Syndrome protein, RECQ4. EMBO J 28, 568-577.
 
Aygün O, Xu X, Liu Y, Takahashi H, Kong SE, Conaway RC, Conaway JW, Svejstrup JQ (2009) Direct inhibition of RNA polymerase II transcription by RECQL5. J Biol Chem 284, 23197-23203.

Liu Y, Conaway JW (2009) When transcription meets recombination: A lesson from the human RECQ protein complexes. F1000 Biology Reports 1, 76.
 
Xu X, Rochette PJ, Feyissa EA, Su TV, Liu Y (2009) MCM10 mediates RECQ4 association with MCM2-7 helicase complex during DNA replication. EMBO J 28, 3005-3014.

Liu Y (2010) Rothmund-Thomson syndrome helicase, RECQ4: On the crossroad between DNA repair and replication. DNA Repair (Amst) 9, 325-330.
 
Li M, Xu X, Liu Y (2011) The Set2-RPB1-interaction domain of human RECQ5 is important for transcription-associated genome maintenance. Mol Cell Biol 31, 2090-2099.

Machwe A, Karale RB, Xu X, Liu Y, Orren DK (2011) The Werner and Bloom syndrome proteins help resolve replication blockage by converting (regressed) Holliday junctions to functional replication forks. Biochemistry 50, 6774-6788.
 
Associate Professor, City of Hope (2011-present)
Hansen JE, Chan G, Liu Y, Hegan DC, Dalal S, Dray E, Kwon Y, Xu Y, Xu X, Peterson-Roth E, Geiger E, Liu Y, Gera J, Sweasy JB, Sung P, Rockwell S, Nishimura RN, Weisbart RH, Glazer PM (2012) Targeting cancer with a lupus autoantibody. Sci Transl Med  4, 157ra142.
 
Wang J, Xu X, Alontaga AY, Chen Y, Liu Y (2014) Impaired p32 regulation caused by the lymphoma-prone RECQ4 mutation drives mitochondrial dysfunction. Cell Reports, in press.
 
Li M, Pokaharel S, Liu Y (2014) Topoisomerase 1 SUMOylated through novel RECQ5 activity couples RNA processing with transcription to prevent R-loop formation. (Manuscript in revision for publication)

Xu X, Wang J, Li M, Liu Y (2014) TIMELESS prevents CDC6-independent assembly of the CDC45-MCM2-7-GINS helicase complex. (Manuscript under review for publication)

 

Laboratory

 
Laboratory
 
The integrity of our chromosomal material is dependent upon the efficient repair of DNA lesions that are caused by exogenous agents, such as UV and ionizing radiation. Without comprehensive DNA repair and surveillance systems, broken chromosomes and mutations accumulate in cells leading to apoptosis, which could have devastating consequences in growth and development of an organism. Lost of genome integrity can also lead to cell transformation, a precursor of cancer development. Many cancer suppressor genes are linked to DNA repair. Therefore, understanding the roles of these cancer suppressor proteins will not only allow us to understand mechanisms of different repair pathways but also how they are regulated and coordinated with each other as caretakers of the genome.

A set of proteins belonging to the RECQ family are among the cancer suppressors linked to DNA repair. During the course of evolution, RECQ genes appear to have been amplified and diverged from a single copy of the RecQ gene in bacteria and yeast to five RECQ homologs in humans. The human RECQ proteins share many similar biochemical properties in vitro and are implicated in many common processes, suggesting they have overlapping functions in vivo. Yet these proteins are not redundant, as mutations in different RECQ proteins lead to different clinical syndromes. So far, BLM, WRN and RECQ4 have been associated with distinct clinical diseases: Bloom syndrome (BS), Werner syndrome (WS) and Rothmund-Thomson syndrome (RTS), respectively. Individuals with BS or RTS exhibit various physical and mental developmental abnormalities, while WS patients’ most striking phenotype is premature aging. Most importantly, all these patients, in particular BS patients, have a high risk of cancer predisposition. As a consequence, cancer is the primary cause of death for BS patients before the age of 30.

The various clinical features shown by individuals with RECQ-related diseases indicate that the human RECQ homologs have evolved to function in distinct pathways to protect the integrity of our genome and ensure proper development. A defect in one RECQ protein is sufficient to cause cell transformation and tumorigenesis, and this defect cannot be compensated by other RECQ proteins. Our long-term agenda is to dissect the functions of individual RECQ proteins in human cells, and these studies will allow us to compare the similarities and differences among the RECQ proteins. Through these comparisons we can then understand what aspects of genome maintenance and DNA metabolism are required for normal development and cancer prevention.

Lab Members:
Xiaohua Xu, Ph.D.
Staff Scientist
626-256-HOPE (4673), ext. 32344
xiaxu@coh.org

Min Li, Ph.D.
Postdoctoral Fellow
626-256-HOPE (4673), ext. 32343
minli@coh.org

Jiin-Tarng Wang, Ph.D.
Postdoctoral Fellow
626-256-HOPE (4673), ext. 32344
jiinwang@coh.org

 
Min-Jung Kang, Ph.D.
Postdoctoral Fellow
626-256-HOPE (4673), ext. 32343
mikang@coh.org
 
Subhash Pokharel
Postdoctoral Fellow
626-256-HOPE (4673), ext. 63324
 

Education

 
Education/Training
  • 1995 - 2000, Yale University, New Haven, CT, Department of Molecular Biophysics and Biochemistry, Ph.D.
  • 1991 - 1995, MIT, Cambridge, MA, Department of Biology, B.S.
 

Professional Experience

 
Career/Academic Appointments
  • 1992-1993 - Research Assistant, Laboratory of Prof. Richard J. Wurtman, MIT Clinical Research Center and Department of Brain and Cognitive Science, Cambridge, MA
  • 1994-1995 - Research Assistant, Laboratory of Prof. Phillips W. Robbins, MIT Center for Cancer Research, Cambridge, MA
  • 1995-2000 Graduate Research Fellow, Laboratory of Prof. Nancy Maizels, Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT
  • 1998 - Teaching Assistant, Department of Molecular Biophysics and Biochemistry graduate course Molecular Genetics of Eukaryotes, Yale University, New Haven, CT
  • 1997-1998 - Teaching Assistant, Department of Molecular Biophysics and Biochemistry graduate course Molecular Genetics of Prokaryotes, Yale University, New Haven, CT
  • 2001-2006 - Postdoctoral Fellow in Biochemistry, Laboratory of Dr. Stephen C. West, Cancer Research UK, Hertfordshire, United Kingdom
  • 2006 - 2011 - Assistant Professor, Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT
  • 2009 - 2011 - Member, Yale Comprehensive Cancer Center
  • 2009 - 2011 - Member, Radiation Research Society
  • 2011- present - Associate Professor, Department of Radiation Biology, Beckman Research Institute, City of Hope, Duarte, CA
  • 2011- present - Associate Chair, Department of Radiation Biology, Beckman Research Institute, City of Hope, Duarte, CA
  • 2011- present - Member, City of Hope Comprehensive Cancer Center
  • 2012 – 2016 - Member, NIH Molecular Genetic Study Section A (MGA)

 

Conferences/Seminars (as invited speaker)

  • Sept, 2000 Department of Molecular Biophysics and Biochemistry Annual Conference, Yale University (Woods Hole, CT)
  • May, 2004 EMBO Workshop: Recombination and Genome Stability - 40th Anniversary Meeting of the Holliday Model (Seilac, France)
  • Jan, 2005 Gordon Research Conference: Mammalian DNA Repair (Ventura, CA)
  • Apr, 2006 Meeting on DNA Repair: from Molecular Mechanism to Human Disease (Noordwijkerhout, The Netherlands)
  • May, 2008 Molecular and Clinical Mechanisms in Bloom’s Syndrome and Related Disorders Workshop (Chicago, Il)
  • May, 2009 ICGEB Conference: Proteomic characterization of macromolecular complexes involved in DNA metabolism (Trieste, Italy)
  • Oct, 2009 Seminar, Vanderbilt Institute of Chemical Biology seminar series, Vanderbilt University, (Nashville, TN)
  • Apr, 2010 The American Society for Biochemistry and Molecular Biology (ASBMB) annual meeting: DNA Transactions (Anaheim, CA)
  • Aug, 2010 Gordon Research Conference in Mutagenesis (Walterville, Maine)
  • Dec, 2010 Seminar, Beckman Research Institute, City of Hope (Duarte, CA)
  • Apr, 2011 Genome Integrity Discussion Group, The New York Academy of Sciences (New York, NY)
  • Oct, 2011 Seminar, Central University & National Taiwan University School of Medicine (Taiwan)
  • March, 2012 Guest lectures and seminar, Zhejiang University (Hangzhou, China)
  • Apr, 2012 Seminar, Saint Louis University School of Medicine (Saint Louis, MO)
  • May, 2012 Seminar, Department of Biochemistry, New York University (New York, NY)
  • June, 2013 Seminar, Department of Chemistry, UC Riverside (Riverside, CA)
  • Jan, 2014 Seminar, Memorial Sloan-Kettering Cancer Center (New York, NY)

Honors/Awards

 
Professional Honors & Recognition
  • 1996-2000 Howard Hughes Medical Institute (HHMI) Pre-doctoral Fellow in Biological Sciences
  • 1998,1999 Department of Molecular Biophysics and Biochemistry Teaching Assistant Awards, Yale University
  • 2000 Winner of the poster presentation ($1,000 cash prize) in 2000 International
  • Symposium on Cancer Research at the Texas Research Park in San Antonio, TX
  • 2001 Imperial Cancer Research Fund Postdoctoral Fellow
  • 2001-2004 American Cancer Society Postdoctoral Fellow
  • 2005-2006 Breast Cancer Campaign Postdoctoral Fellow
  • 2008-2009 Breast Cancer Alliance Young Investigator Award