Homologous recombination research is heating up and ready for therapy - PubMed (original) (raw)

Comment

Homologous recombination research is heating up and ready for therapy

Simon N Powell et al. Proc Natl Acad Sci U S A. 2011.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.

DSBs in S and G2 phases of the cell cycle, collapsed replication forks, and daughter-strand gaps all require HR for their repair. The effect of mild hyperthermia does not affect the ability of first responders, such as recruiting the Mre11 complex at DSB or RP-A binding to single-strand DNA. However, the recruitment of BRCA2 and RAD51 is affected, suggesting that somewhere in the HR pathway, there is susceptibility to heat-induced protein degradation. Although Krawczyk et al. (1) suggest that the target is BRCA2, it could be at multiple points along the BRCA2 pathway of HR, including BRCA1 and PALB2. In the absence of the key RP-A-to-RAD51 mediator, BRCA2, there is failure to carry out HR as observed by reduced RAD51 foci and reduced sister chromatid exchanges.

Comment on

Mild hyperthermia inhibits homologous recombination, induces BRCA2 degradation, and sensitizes cancer cells to poly (ADP-ribose) polymerase-1 inhibition.
Krawczyk PM, Eppink B, Essers J, Stap J, Rodermond H, Odijk H, Zelensky A, van Bree C, Stalpers LJ, Buist MR, Soullié T, Rens J, Verhagen HJ, O'Connor MJ, Franken NA, Ten Hagen TL, Kanaar R, Aten JA. Krawczyk PM, et al. Proc Natl Acad Sci U S A. 2011 Jun 14;108(24):9851-6. doi: 10.1073/pnas.1101053108. Epub 2011 May 9. Proc Natl Acad Sci U S A. 2011. PMID: 21555554 Free PMC article.

References

1. Krawczyk PM, et al. Mild hyperthermia inhibits homologous recombination, induces BRCA2 degradation, and sensitizes cancer cells to poly(ADP-ribose) polymerase-1 inhibition. Proc Natl Acad Sci USA. 2011;108:9851–9856. - PMC - PubMed
1. Wanner RA, Edwards MJ, Wright RG. The effect of hyperthermia on the neuroepithelium of the 21-day guinea-pig foetus: Histologic and ultrastructural study. J Pathol. 1976;118:235–244. - PubMed
1. Dewey WC, Hopwood LE, Sapareto SA, Gerweck LE. Cellular responses to combinations of hyperthermia and radiation. Radiology. 1977;123:463–474. - PubMed
1. VanderWaal RP, Griffith CL, Wright WD, Borrelli MJ, Roti JL. Delaying S-phase progression rescues cells from heat-induced S-phase hypertoxicity. J Cell Physiol. 2001;187:236–243. - PubMed
1. Arora D, Skliar M, Roemer RB. Model-predictive control of hyperthermia treatments. IEEE Trans Biomed Eng. 2002;49:629–639. - PubMed

Homologous recombination research is heating up and ready for therapy - PubMed (original) (raw)