Dr. Yue Zou

Dr. Yue Zou

Yue Zou, Ph.D.

Professor 


Contact Information:
J. H. Quillen College of Medicine, ETSU
Department of Biomedical Sciences 
Box 70581, Johnson City TN 37614

Phone:  Lab-(423) 439-2123
            Office-(423) 439-2124
FAX: (423) 439-2030
email:  

  Room B029, Building 178, VA Campus

Education
  • 1982    B.S.      Chengdu University of Sci. and Tech. , China
  • 1985    M.S.     Dalian Institute of Chemical Physics, CAS, China

  • 1991    Ph.D.   Clark University , Worcester , Massachusetts


Research Interests


Research interests of my laboratory focus on mechanistic understanding of DNA damage, repair, and checkpoints, as well as the interactions between these pathways. Today one of the greatest challenges to the human health today is the voluntary and involuntary exposure to a variety of ubiquitous genotoxic agents (typically UV irradiation and environmental carcinogens) which potentially cause DNA damage, mutations, genome instability and thus cancers. To cope with genetic stress induced by DNA damage, cells launch a series of cellular responses primarily including DNA repair and DNA damage checkpoints. As a cellular defense system against DNA damage for maintaining the integrity of genetic materials, DNA repair recognizes and removes DNA lesions, while activation of DNA damage checkpoints leads to the arrest of cell cycle progression to allow sufficient time for DNA repair. Nucleotide excision repair (NER) is one of the major DNA repair pathways in cells. It removes a large variety of DNA lesions induced by various environmental pollutants and carcinogens. We are particularly interested in DNA damage recognition, structure and function of repair proteins, and the relationship of NER with DNA damage checkpoints, particularly ATR and ATM signaling pathways. Our work includes characterization of xeroderma pigmentosum group A (XPA) and replication protein A (RPA) for their role in NER and checkpoint regulation in cellular responses to DNA damage. In addiction, the involvement of NER in removal of a variety of carcinogenic DNA adducts has been examined.

Another major effort in my lab is to determine the molecular basis of DNA damage, particularly DNA double-strand breaks (DSBs), accumulation in laminopathy-based premature aging and normal aging. While aging that governs human lifespan is a normal but complex biological process, individuals who have the rare disease Hutchinson-Gilford progeria syndrome (HGPS) suffer from premature aging. Recent evidence links HGPS to deficiency in maturation of lamin A protein, a major inner component of the nuclear envelope and skeleton. The accelerated aging phenotypes may result from genomic instability induced by DSB accumulation, an observation similar to that in normal aging. However, how these DSBs form as the result of the lamin A deficiency and why they are resistant to repair and thus accumulate remain unknown. Our goal is to delineate the underlying mechanism and its potential implication in normal aging. Such understanding may provide molecular basis for development of potential new therapeutic strategies for better treatment of the devastating disease. 

Selected References

1:

Other proteins interacting with XP proteins.

 

Shell SM, Zou Y.
Adv Exp Med Biol. 2008;637:103-12. No abstract available.
PMID: 19181115 [PubMed - in process]
Related Articles

2:

Involvement of xeroderma pigmentosum group A (XPA) in progeria arising from defective maturation of prelamin A.

 

Liu Y, Wang Y, Rusinol AE, Sinensky MS, Liu J, Shell SM, Zou Y.
FASEB J. 2008 Feb;22(2):603-11. Epub 2007 Sep 11.
PMID: 17848622 [PubMed - indexed for MEDLINE]
Related Articles Free article at journal site

3:

Structural characterization of human RPA sequential binding to single-stranded DNA using ssDNA as a molecular ruler.

 

Cai L, Roginskaya M, Qu Y, Yang Z, Xu Y, Zou Y.
Biochemistry. 2007 Jul 17;46(28):8226-33. Epub 2007 Jun 21.
PMID: 17583916 [PubMed - indexed for MEDLINE]
Related Articles Free article in PMC | at journal site

4:

Specific and efficient binding of xeroderma pigmentosum complementation group A to double-strand/single-strand DNA junctions with 3'- and/or 5'-ssDNA branches.

 

Yang Z, Roginskaya M, Colis LC, Basu AK, Shell SM, Liu Y, Musich PR, Harris CM, Harris TM, Zou Y.
Biochemistry. 2006 Dec 26;45(51):15921-30. Epub 2006 Dec 19.
PMID: 17176115 [PubMed - indexed for MEDLINE]
Related Articles Free article in PMC | at journal site

5:

DNA damage responses in progeroid syndromes arise from defective maturation of prelamin A.

 

Liu Y, Rusinol A, Sinensky M, Wang Y, Zou Y.
J Cell Sci. 2006 Nov 15;119(Pt 22):4644-9. Epub 2006 Oct 24.
PMID: 17062639 [PubMed - indexed for MEDLINE]
Related Articles Free article at journal site

6:

ATR-dependent checkpoint modulates XPA nuclear import in response to UV irradiation.

 

Wu X, Shell SM, Liu Y, Zou Y.
Oncogene. 2007 Feb 1;26(5):757-64. Epub 2006 Jul 24.
PMID: 16862173 [PubMed - indexed for MEDLINE]
Related Articles

7:

Phosphorylation of nucleotide excision repair factor xeroderma pigmentosum group A by ataxia telangiectasia mutated and Rad3-related-dependent checkpoint pathway promotes cell survival in response to UV irradiation.

 

Wu X, Shell SM, Yang Z, Zou Y.
Cancer Res. 2006 Mar 15;66(6):2997-3005.
PMID: 16540648 [PubMed - indexed for MEDLINE]
Related Articles Free article in PMC | at journal site

8:

Functions of human replication protein A (RPA): from DNA replication to DNA damage and stress responses.

 

Zou Y, Liu Y, Wu X, Shell SM.
J Cell Physiol. 2006 Aug;208(2):267-73. Review.
PMID: 16523492 [PubMed - indexed for MEDLINE]
Related Articles

9:

A quantitative analysis of secondary RNA structure using domination based parameters on trees.

 

Haynes T, Knisley D, Seier E, Zou Y.
BMC Bioinformatics. 2006 Mar 3;7:108.
PMID: 16515683 [PubMed - indexed for MEDLINE]
Related Articles Free article in PMC | at journal site

10:

Recognition and incision of gamma-radiation-induced cross-linked guanine-thymine tandem lesion G[8,5-Me]T by UvrABC nuclease.

 

Yang Z, Colis LC, Basu AK, Zou Y.
Chem Res Toxicol. 2005 Sep;18(9):1339-46.
PMID: 16167825 [PubMed - indexed for MEDLINE]
Related Articles

11:

Modulation of replication protein A function by its hyperphosphorylation-induced conformational change involving DNA binding domain B.

 

Liu Y, Kvaratskhelia M, Hess S, Qu Y, Zou Y.
J Biol Chem. 2005 Sep 23;280(38):32775-83. Epub 2005 Jul 9.
PMID: 16006651 [PubMed - indexed for MEDLINE]
Related Articles Free article in PMC | at journal site

12:

Preferential localization of hyperphosphorylated replication protein A to double-strand break repair and checkpoint complexes upon DNA damage.

 

Wu X, Yang Z, Liu Y, Zou Y.
Biochem J. 2005 Nov 1;391(Pt 3):473-80.
PMID: 15929725 [PubMed - indexed for MEDLINE]
Related Articles Free article in PMC | at journal site

13:

Interaction and colocalization of Rad9/Rad1/Hus1 checkpoint complex with replication protein A in human cells.

 

Wu X, Shell SM, Zou Y.
Oncogene. 2005 Jul 7;24(29):4728-35.
PMID: 15897895 [PubMed - indexed for MEDLINE]
Related Articles Free article in PMC | at journal site

14:

Cooperative interaction of human XPA stabilizes and enhances specific binding of XPA to DNA damage.

 

Liu Y, Liu Y, Yang Z, Utzat C, Wang G, Basu AK, Zou Y.
Biochemistry. 2005 May 17;44(19):7361-8.
PMID: 15882075 [PubMed - indexed for MEDLINE]
Related Articles Free article in PMC | at journal site

15:

Mass spectrometric identification of lysines involved in the interaction of human replication protein a with single-stranded DNA.

 

Shell SM, Hess S, Kvaratskhelia M, Zou Y.
Biochemistry. 2005 Jan 25;44(3):971-8.
PMID: 15654753 [PubMed - indexed for MEDLINE]
Related Articles Free article in PMC | at journal site

16:

Interactions of human replication protein A with single-stranded DNA adducts.

 

Liu Y, Yang Z, Utzat CD, Liu Y, Geacintov NE, Basu AK, Zou Y.
Biochem J. 2005 Jan 15;385(Pt 2):519-26.
PMID: 15362978 [PubMed - indexed for MEDLINE]
Related Articles Free article in PMC | at journal site

17:

Thermodynamic characterization of the interaction of mutant UvrB protein with damaged DNA.

 

Ma H, Zou Y.
Biochemistry. 2004 Apr 13;43(14):4206-11.
PMID: 15065864 [PubMed - indexed for MEDLINE]
Related Articles Free article in PMC | at journal site

18:

DNA damage recognition of mutated forms of UvrB proteins in nucleotide excision repair.

 

Zou Y, Ma H, Minko IG, Shell SM, Yang Z, Qu Y, Xu Y, Geacintov NE, Lloyd RS.
Biochemistry. 2004 Apr 13;43(14):4196-205. Erratum in: Biochemistry. 2004 Jun 1;43(21):6832.
PMID: 15065863 [PubMed - indexed for MEDLINE]
Related Articles Free article in PMC | at journal site

19:

Effects of DNA adduct structure and sequence context on strand opening of repair intermediates and incision by UvrABC nuclease.

 

Zou Y, Shell SM, Utzat CD, Luo C, Yang Z, Geacintov NE, Basu AK.
Biochemistry. 2003 Nov 4;42(43):12654-61.
PMID: 14580212 [PubMed - indexed for MEDLINE]
Related Articles Free article in PMC | at journal site

20:

Dimerization of human XPA and formation of XPA2-RPA protein complex.

 

Yang ZG, Liu Y, Mao LY, Zhang JT, Zou Y.
Biochemistry. 2002 Oct 29;41(43):13012-20.
PMID: 12390028 [PubMed - indexed for MEDLINE]
Related Articles Free article in PMC | at journal site