The mismatch DNA repair heterodimer, hMSH2/6, regulates BLM helicase
Authors: Sagar Sengupta
Susan J Littman
Steven P Linke
Curtis C Harris
Graziella Pedrazzi
Qin Yang
Ran Zhang
Paul Modrich
Claudia Perrera
Xin W Wang
Ian D Hickson
Igor Stagljar
Journal: Oncogene (2004)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: MSH2/6 complex; mismatch recognition; DNA repair; homologous recombination; BLM
Affiliations: Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bldg 37, Rm 3068, 37 Convent Drive, Bethesda, MD 20892-4255, USA.

Abstract:  The human MSH2/6 complex is essential for mismatch recognition during the repair of replication errors. Although mismatch repair components have been implicated in DNA homologous recombination repair, the exact function of hMSH2/6 in this pathway is unclear. Here, we show that the recombinant hMSH2/6 protein complex stimulated the ability of the Bloom's syndrome gene product, BLM, to process Holliday junctions in vitro, an activity that could also be regulated by p53. Consistent with these observations, hMSH6 colocalized with BLM and phospho-ser15-p53 in hydroxyurea-induced RAD51 nuclear foci that may correspond to the sites of presumed stalled DNA replication forks and more likely the resultant DNA double-stranded breaks. In addition, we show that hMSH2 and hMSH6 coimmunoprecipitated with BLM, p53, and RAD51. Both the number of RAD51 foci and the amount of the BLM-p53-RAD51 complex are increased in hMSH2- or hMSH6-deficient cells. These data suggest that hMSH2/6 formed a complex with BLM-p53-RAD51 in response to the damaged DNA forks during double-stranded break repair. 

Retracted: No

PubPeer comments:
 Figure 4c. Much more similar than expected. ![file] , 
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 #2 Thank you for your reply. Could the authors please provide a high resolution version of the original uncropped scans? You may post those here or use a link to an external site (such as Imgur.com or Google Drive) for larger files. , 
 #3 We do not have these original images from this more than 15 year old study. Careful analysis of the published images was described above showing similarity but not identical. , 
 #4 Respectfully: it is possible that the images highlighted in #1 are different images, but without the original data, I still have concerns. The authors may wish to read [this post ] which illustrates the impact of image compression which may be a factor here. It is the similarities that concern me (which are numerous), not the differences (which are few). My own careful analysis includes a few techniques and tools I and others use, examples below. Other readers may wish to chime in. *** False color ![file] *** Inverse ![file] *** Forensically clone tool ![file] , 
 #4  Careful analysis of the published images was described ... 2 arrows, but it is not obvious what they are pointing at. Could the authors illustrate where the differences are? , 
 #3 We have a higher resolution image, its too large to post it here, please use the link to download, and let us know if this is satisfactory. Thank you ver y much. https: drive.google.com file d 1sdfVhXboXEmlwNXHV_xK49HuTOlNgH5W view?usp=sharing , 
 #7 Thank you very much for providing the high resolution file. Using this, I have overlaid an inverted image on top of the original image and shifted the inverted image 2 lanes to the right so the smears line up. As you can see below, the inverse smears completely cancel out the uninverted smears. This is highly suggestive that these two sets of smears derive from the same source. ![file] , 
 Yes they were happy with the analysis provided to show differences Kind Regards Lucinda Lucinda Haines Senior Publishing Manager Springer Nature The Campus | 4 Crinan Street |London |N1 9XW |UK T: +44 (0) 207 843 3634 We had the editors of ONCOGENE analyze the western and the enlarged comparison of the two bands is question. As you can read above, they concluded independently that they were different. , 
 #9  We had the editors of ONCOGENE analyze the western and the enlarged comparison of the two bands is question. As you can read above, they concluded independently that they were different. How many editors were involved? Could the editors post their independent analyses here? , 
 #9  We had the editors of ONCOGENE analyze the western and the enlarged comparison of the two bands is question. As you can read above, they concluded independently that they were different. 1 of 2 Editors ONCOGENE was unable to detect problematic data in his own publication. https: academic.oup.com nar article 49 20 12006 6414044 Nucleic Acids Research, Volume 37, Issue 9, 1 May 2009, Pages 3110u20133123, https: doi.org 10.1093 nar gkp136 Following initial allegations of image manipulation in 2017 in the above article (1) the journal investigated the matter and did not find conclusive evidence to support the allegations. When further allegations were raised in 2021, the journal referred the matter to the authorsu2019 institutions and an Expression of Concern was published in NAR (2). The Editors of the journal are now retracting the article for the following reasons: The authors have been unable to produce the original raw image files for either the journal or the institutions. The authorsu2019 institutions conducted a formal investigation, and the official report dated 26-Aug-2021 concludes: u2018although the results themselves are not in question (having been verified by the subsequent repeat experiments carried out by the authors), the paper should still be retracted on the basis that the original data is no longer available, and was not available in 2017 when these concerns were first raised.u2019 REFERENCES 1.tGiamas G., Castellano L., Feng Q., Knippschild U., Jacob J., Thomas R.S., Coombes R.C., Smith C.L., Jiao L.R., Stebbing J. CK1u03b4 modulates the transcriptional activity of ERu03b1 via AIB1 in an estrogen-dependent manner and regulates ERu03b1u2013AIB1 interactions. Nucleic Acids Res. 2009; 37:3110u20133123. 2.tFox K.R., Stoddard B.L. Editorial Expression of Concern on article u2018CK1u03b4 modulates the transcriptional activity of ERu03b1 via AIB1 in an estrogen-dependent manner and regulates ERu03b1u2013AIB1 interactionsu2019. Nucleic Acids Res. 2021; 49:3602. ,