Article

It takes a PHD to SUMO.

Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Trends in Biochemical Sciences (Impact Factor: 13.52). 06/2008; 33(5):191-4. DOI: 10.1016/j.tibs.2008.02.003
Source: PubMed

ABSTRACT PHD fingers and bromodomains are found in close proximity to each other in many chromatin-associated proteins and can functionally synergize. Recently, it has been demonstrated that the PHD finger of the KAP1 co-repressor functions as an E3 SUMO ligase for the adjacent bromodomain. This PHD-mediated SUMOylation stabilizes the association of the bromodomain with the chromatin modifiers SETDB1 and the nucleosome remodeling and deacetylation (NuRD) complex, thereby promoting establishment of the silent gene expression state.

0 Followers
 · 
72 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mutations can be beneficial under conditions in which genetic diversity is advantageous, such as somatic hypermutation and antibody generation, but they can also be lethal when they disrupt basic cellular processes or cause uncontrolled proliferation and cancer. Mutations arise from inaccurate processing of lesions generated by endogenous and exogenous DNA damaging agents, and the genome is particularly vulnerable to such damage during S phase. In this phase of the cell cycle, many lesions in the DNA template block replication. Such lesions must be bypassed in order to preserve fork stability and to ensure completion of DNA replication. Lesion bypass is carried out by a set of error-prone and error-free processes collectively referred to as DNA damage tolerance mechanisms. Here, we discuss how two types of DNA damage tolerance, translesion synthesis and template switching, are regulated at stalled replication forks by ubiquitination of PCNA, and the conditions under which they occur.
    Nature Chemical Biology 03/2009; 5(2):82-90. DOI:10.1038/nchembio.139 · 13.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We report a sensitive peptide pull-down approach in combination with protein identification by LC-MS/MS and qualitative abundance measurements by spectrum counting to identify proteins binding to histone H3 tail containing dimethyl lysine 4 (H3K4me2), dimethyl lysine 9 (H3K9me2), or acetyl lysine 9 (H3K9ac). Our study identified 86 nuclear proteins that associate with the histone H3 tail peptides examined, including seven known direct binders and 16 putative direct binders with conserved PHD finger, bromodomain, and WD40 domains. The reliability of our proteomic screen is supported by the fact that more than one-third of the proteins identified were previously described to associate with histone H3 tail directly or indirectly. To our knowledge, the results presented here are the most comprehensive analysis of H3K4me2, H3K9me2, and H3K9ac associated proteins and will provide a useful resource for researchers studying the mechanisms of histone code effector proteins.
    Proteomics 05/2009; 9(9):2343-54. DOI:10.1002/pmic.200800600 · 3.97 Impact Factor
  • Journal of Cell Science 12/2009; 122(Pt 23):4249-52. DOI:10.1242/jcs.050542 · 5.33 Impact Factor