Cell Apoptosis: Requirement of H2AX in DNA Ladder Formation, but Not for the Activation of Caspase-3

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2006 Jul 5

PMID 16818236

Citations 178

Authors

Chengrong Lu

Feng Zhu

Yong-Yeon Cho

Faqing Tang

Tatyana Zykova

Wei-Ya Ma

Ann M Bode

Zigang Dong

Affiliations

Soon will be listed here.

Abstract

Immunofluorescence studies have revealed that H2AX is phosphorylated at the sites of DNA double-strand breaks induced by ionizing radiation and is required for recruitment of repair factors into nuclear foci after DNA damage. Therefore, the function of H2AX is believed to be associated primarily with repair of DNA damage. Here, we report a function of H2AX in cellular apoptosis. Our data showed that H2AX is phosphorylated by UVA-activated JNK. We also provided evidence showing that UVA induces caspase-3 and caspase-activated DNase (CAD) activity in both H2AX wild-type and H2AX knockout mouse embryonic fibroblasts (MEFs). However, DNA fragmentation occurred only in H2AX wild-type MEFs. Furthermore, H2AX phosphorylation was critical for DNA degradation triggered by CAD in vitro. Taken together, these data indicated that H2AX phosphorylation is required for DNA ladder formation, but not for the activation of caspase-3; and the JNK/H2AX pathway cooperates with the caspase-3/CAD pathway resulting in cellular apoptosis.

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