Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest

Sagar Sengupta, Ana I. Robles, Steven P. Linke, Natasha I. Sinogeeva, Ran Zhang, Remy Pedeux, Irene M. Ward, Arkady Celeste, André Nussenzweig, Junjie Chen, Thanos D. Halazonetis, Curtis C. Harris

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Bloom's syndrome is a rare autosomal recessive genetic disorder characterized by chromosomal aberrations, genetic instability, and cancer predisposition, all of which may be the result of abnormal signal transduction during DNA damage recognition. Here, we show that BLM is an intermediate responder to stalled DNA replication forks. BLM colocalized and physically interacted with the DNA damage response proteins 53BP1 and H2AX. Although BLM facilitated physical interaction between p53 and 53BP1, 53BP1 was required for efficient accumulation of both BLM and p53 at the sites of stalled replication. The accumulation of BLM/53BP1 foci and the physical interaction between them was independent of γ-H2AX. The active Chk1 kinase was essential for both the accurate focal colocalization of 53BP1 with BLM and the consequent stabilization of BLM. Once the ATR/Chk1- and 53BP1-mediated signal from replicational stress is received, BLM functions in multiple downstream repair processes, thereby fulfilling its role as a caretaker tumor suppressor.

Original languageEnglish (US)
Pages (from-to)801-813
Number of pages13
JournalJournal of Cell Biology
Volume166
Issue number6
DOIs
StatePublished - Sep 13 2004

Fingerprint

S Phase
DNA Damage
Bloom Syndrome
Inborn Genetic Diseases
DNA Replication
Chromosome Aberrations
Signal Transduction
Neoplasms
Checkpoint Kinase 1
Tumor Suppressor p53-Binding Protein 1

Keywords

  • Homologous recombination
  • Replication arrest
  • Signal transduction
  • p53
  • γ-H2AX

ASJC Scopus subject areas

  • Cell Biology

Cite this

Sengupta, S., Robles, A. I., Linke, S. P., Sinogeeva, N. I., Zhang, R., Pedeux, R., ... Harris, C. C. (2004). Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest. Journal of Cell Biology, 166(6), 801-813. https://doi.org/10.1083/jcb.200405128

Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest. / Sengupta, Sagar; Robles, Ana I.; Linke, Steven P.; Sinogeeva, Natasha I.; Zhang, Ran; Pedeux, Remy; Ward, Irene M.; Celeste, Arkady; Nussenzweig, André; Chen, Junjie; Halazonetis, Thanos D.; Harris, Curtis C.

In: Journal of Cell Biology, Vol. 166, No. 6, 13.09.2004, p. 801-813.

Research output: Contribution to journalArticle

Sengupta, S, Robles, AI, Linke, SP, Sinogeeva, NI, Zhang, R, Pedeux, R, Ward, IM, Celeste, A, Nussenzweig, A, Chen, J, Halazonetis, TD & Harris, CC 2004, 'Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest', Journal of Cell Biology, vol. 166, no. 6, pp. 801-813. https://doi.org/10.1083/jcb.200405128
Sengupta, Sagar ; Robles, Ana I. ; Linke, Steven P. ; Sinogeeva, Natasha I. ; Zhang, Ran ; Pedeux, Remy ; Ward, Irene M. ; Celeste, Arkady ; Nussenzweig, André ; Chen, Junjie ; Halazonetis, Thanos D. ; Harris, Curtis C. / Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest. In: Journal of Cell Biology. 2004 ; Vol. 166, No. 6. pp. 801-813.
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