MiR-24-mediated downregulation of H2AX suppresses DNA repair in terminally differentiated blood cells

Ashish Lal, Yunfeng Pan, Francisco Navarro, Derek M. Dykxhoorn, Lisa Moreau, Eti Meire, Zvi Bentwich, Judy Lieberman, Dipanjan Chowdhury

Research output: Contribution to journalArticlepeer-review

227 Scopus citations


Terminally differentiated cells have a reduced capacity to repair double-stranded breaks, but the molecular mechanism behind this downregulation is unclear. Here we find that miR-24 is upregulated during postmitotic differentiation of hematopoietic cell lines and regulates the histone variant H2AX, a protein that has a key role in the double-stranded break response. We show that the H2AX 3′ untranslated region contains conserved miR-24 binding sites that are indeed regulated by miR-24. During terminal differentiation, both H2AX mRNA and protein levels are substantially reduced by miR-24 upregulation in in vitro differentiated cells; similar diminished levels are found in primary human blood cells. miR-24-mediated suppression of H2AX renders cells hypersensitive to γ-irradiation and genotoxic drugs, a phenotype that is fully rescued by overexpression of miR-24-insensitive H2AX. Therefore, miR-24 upregulation in postreplicative cells reduces H2AX and makes them vulnerable to DNA damage.

Original languageEnglish (US)
Pages (from-to)492-498
Number of pages7
JournalNature Structural and Molecular Biology
Issue number5
StatePublished - May 2009
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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