Intra-nuclear trafficking of the BLM helicase to DNA damage-induced foci is regulated by SUMO modification Journal Article
| Authors: | Eladad, S.; Ye, T. Z.; Hu, P.; Leversha, M.; Beresten, S.; Matunis, M. J.; Ellis, N. A. |
| Article Title: | Intra-nuclear trafficking of the BLM helicase to DNA damage-induced foci is regulated by SUMO modification |
| Abstract: | The Bloom syndrome gene, BLM, encodes a RecQ DNA helicase that when absent from the cell results in genomic instability and cancer predisposition. We show here that BLM is a substrate for small ubiquitin-like modifier (SUMO) modification, with lysines at K317, K331, K334 and K347 being preferred sites of modification. Unlike normal BLM, a double mutant BLM protein with lysine to arginine substitutions at residues 317 and 331 was not modified by SUMO, and it failed to localize efficiently to the PML nuclear bodies. Rather, double mutant BLM protein induced the formation of DNA damage-induced foci (DDI) that contained BRCA1 protein and phosphorylated histone H2AX. Double mutant BLM only partially complemented the genomic instability phenotypes of Bloom syndrome cells as assessed by sister-chromatid exchange and micronuclei formation assays. These results constitute evidence that BLM is a DNA damage sensor that signals the formation of DDI, and they establish SUMO modification as a negative regulator of BLM's signaling function. © The Author 2005. Published by Oxford University Press. All rights reserved. |
| Keywords: | signal transduction; controlled study; protein phosphorylation; unclassified drug; human cell; mutation; protein localization; phenotype; dna damage; cancer susceptibility; amino acid substitution; brca1 protein; chromatid; leukemia, promyelocytic, acute; fluorescent antibody technique; dna; regulatory mechanism; genomic instability; nucleotide sequence; protein transport; promyelocytic leukemia; protein structure, tertiary; cell nucleus; helicase; sumo protein; sumo-1 protein; histone h2a; adenosine triphosphatases; dna helicases; lysine; arginine; mutant; protein modification; cell nucleus inclusion body; bloom syndrome; protein blm |
| Journal Title: | Human Molecular Genetics |
| Volume: | 14 |
| Issue: | 10 |
| ISSN: | 0964-6906 |
| Publisher: | Oxford University Press |
| Date Published: | 2005-05-15 |
| Start Page: | 1351 |
| End Page: | 1365 |
| Language: | English |
| DOI: | 10.1093/hmg/ddi145 |
| PUBMED: | 15829507 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 60" - "Export Date: 24 October 2012" - "CODEN: HMGEE" - "Molecular Sequence Numbers: GENBANK: AF015308, D67025, NM_006950, U29092, U49056, U83117, X99585;" - "Source: Scopus" |
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