Review

Damaged-DNA Binding Protein-2 Drives Apoptosis Following DNA Damage

Srilata Bagchi¹ and Pradip Raychaudhuri^2*

• * Corresponding author: Pradip Raychaudhuri pradip@uic.edu

Author Affiliations

¹ Center of Molecular Biology of Oral Diseases (M/C 860), College of Dentistry, Cancer Center, University of Illinois at Chicago, 801 S. Paulina Ave, Chicago, IL-60612, USA

² Department of Biochemistry and Molecular Genetics (M/C 669), Cancer Center, University of Illinois at Chicago, 900 S. Ashland Ave, Chicago, IL-60607, USA

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Cell Division 2010, 5:3 doi:10.1186/1747-1028-5-3

Published: 19 January 2010

Abstract

Apoptosis induced by DNA damage is an important mechanism of tumor suppression and it is significant also in cancer chemotherapy. Mammalian cells activate the pathways of p53 to induce apoptosis of cells harboring irreparable DNA damages. While p53 induces expression of various pro-apoptotic genes and directly participates in the disruption of mitochondrial membrane polarization, it also increases expression of the cell cycle inhibitor p21 that is a dominant inhibitor of caspase-activation and apoptosis. Here we discuss how Damaged-DNA Binding Protein-2 (DDB2) subdues the level of p21 in cells harboring irreparable DNA damage to support activation of the caspases. We speculate a model in which DDB2 detects and couples the presence of un-repaired DNA damages to the proteolysis of p21, leading to the induction of apoptosis.