Clld7, a candidate tumor suppressor on chromosome 13q14, regulates pathways of DNA damage/repair and apoptosis

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BlankClld7, a candidate tumor suppressor on chromosome 13q14, regulates pathways

of DNA damage/repair and apoptosis

1.. Xiaobo Zhou1,* and

2.. Karl Münger2

+ Author Affiliations

1.. 1Medicine, Brigham and Women's Hospital

2.. 2Dept of Medicine, Brigham & Women's Hospital/HMS

1.. * Corresponding Author:

Xiaobo Zhou, Medicine, Brigham and Women's Hospital, Channing laboratory, 181

Longwood Avenue, Boston, 02115, United States xzhou@...

Abstract

Chronic lymphocytic leukemia deletion gene 7 (Clld7) is a candidate tumor

suppressor on chromosome 13q14. Clld7 encodes an evolutionarily conserved

protein that contains an RCC1 domain plus broad complex, tramtrack, bric-a-brac

(BTB) and POZ domains. In this study, we investigated the biological functions

of Clld7 protein in inducible osteosarcoma cell lines. Clld7 induction inhibited

cell growth, decreased cell viability, and increased gamma-H2AX staining under

conditions of caspase inhibition, indicating activation of the DNA damage/repair

pathway. Real-time PCR analysis in tumor cells and normal human epithelial cells

revealed Clld7 target genes that regulate DNA repair responses. Furthermore,

depletion of Clld7 in normal human epithelial cells conferred resistance to

apoptosis triggered by DNA damage. Taken together, the biological actions of

Clld7 are consistent with those of a tumor suppressor.

a.. Received May 31, 2010.

b.. Revision received September 10, 2010.

c.. Accepted September 22, 2010.