Regulation and localization of the Bloom syndrome protein in response to DNA damage

Oliver Bischof, Sahn Ho Kim, John Irving, Sergey Beresten, Nathan A. Ellis, Judith Campisi

Research output: Contribution to journalArticlepeer-review

227 Scopus citations

Abstract

Bloom syndrome (BS) is an autosomal recessive disorder characterized by a high incidence of cancer and genomic instability. BLM, the protein defective in BS, is a RecQ-like helicase, presumed to function in DNA replication, recombination, or repair. BLM localizes to promyelocytic leukemia protein (PML) nuclear bodies and is expressed during late S and G2. We show, in normal human cells, that the recombination/ repair proteins hRAD51 and replication protein (RP)-A assembled with BLM into a fraction of PML bodies during late S/G2. Biochemical experiments suggested that BLM resides in a nuclear matrix - bound complex in which association with hRAD51 may be direct. DNA-damaging agents that cause double strand breaks and a G2 delay induced BLM by a p53- and ataxia-telangiectasia mutated independent mechanism. This induction depended on the G2 delay, because it failed to occur when G2 was prevented or bypassed. It coincided with the appearance of foci containing BLM, PML, hRAD51 and RP-A, which resembled ionizing radiation-induced foci. After radiation, foci containing BLM and PML formed at sites of single-stranded DNA and presumptive repair in normal cells, but not in cells with defective PML. Our findings suggest that BLM is part of a dynamic nuclear matrix - based complex that requires PML and functions during G2 in undamaged cells and recombinational repair after DNA damage.

Original languageEnglish (US)
Pages (from-to)367-380
Number of pages14
JournalJournal of Cell Biology
Volume153
Issue number2
DOIs
StatePublished - Apr 16 2001

Keywords

  • ATM
  • Homologous recombination
  • Nuclear matrix
  • RECQ helicases
  • p53

ASJC Scopus subject areas

  • Cell Biology

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