Disease relevance of Chromatids

• NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome [1].
• Here, we report that cells doubly deficient for telomerase and WRN helicase show chromosomal aberrations and elevated recombination rates between telomeres of sister chromatids [2].
• METHODS: Mutagen sensitivity (mean number of chromatid breaks per cell of cultured lymphocytes treated with bleomycin in the late S-G2 phase of the cell cycle) was determined in 313 patients with head and neck cancer and in 334 control subjects at two major U.S. medical institutions and one European institution, yielding a unique study population [3].
• The cells from individuals with DNS or hereditary cutaneous malignant melanoma with DNS (HCMM/DNS) had significantly more chromatid breaks and gaps when entering metaphase 0.5-1.5 h after G2 phase X-irradiation (1 Gy) than those from unaffected controls [4].
• The mammalian securin, pituitary tumor transforming gene (PTTG), regulates sister chromatid separation during mitosis [5].

High impact information on Chromatids

• Cleavage of cohesin's kleisin subunit by the separase protease then triggers the movement of sister chromatids into opposite halves of the cell during anaphase [6].
• The separation of sister chromatids at the metaphase-to-anaphase transition is triggered by a protease called separase that is activated by the destruction of an inhibitory chaperone (securin) [7].
• The yeast APC/C subunit Mnd2 prevents premature sister chromatid separation triggered by the meiosis-specific APC/C-Ama1 [8].
• Phosphorylation of separase recognition sites may be highly conserved and regulates sister chromatid separation independently of securin [9].
• Phosphorylation of the cohesin subunit Scc1 by Polo/Cdc5 kinase regulates sister chromatid separation in yeast [9].

Chemical compound and disease context of Chromatids

• After in vitro incubation with bromodeoxyuridine (BrdUrd)-containing medium, metaphases of Philadelphia (Ph1)-chromosome positive cells in the blood and/or bone marrow of eight untreated patients with chronic myelocytic leukemia (CML) were analysed by means of sister chromatid differentiation (SCD) and compared to 10 normal bone marrows [10].
• In Fanconi's anemia and in normal cells after Trenimon-treatment, the majority of chromatid translocations are between nonhomologous chromosomes, whereas in Bloom's syndrome mainly homologous chromosomes are involved [11].
• The frequencies of caffeine-induced chromosomal aberrations (CA), mainly chromatid (CdB) and chromosome (CB) breaks, were studied in lymphocyte cultures derived from 6 obligatory heterozygotes and 1 homozygote of ataxia telangiectasia (AT), and from 4 control adult healthy persons [12].
• Enhancement of frequencies of restriction endonuclease-induced chromatid breaks by arabinoside adenine in normal human and ataxia telangiectasia cells [13].
• Paracetamol (1 mM for 2 h) also increased the number of chromosomal aberrations CAs in wild-type cells (i.e. chromatid breaks and chromatid exchanges) [14].

Biological context of Chromatids

• The unique features of prezygotene chromosomes are a partial separation of sister chromatids, an elongation of knob heterochromatin, an increase in surface complexity, a 50% increase in total chromosome volume, and a peripheral localization and alignment of telomeric, but not proximal, loci [15].
• Proteolytic cleavage of cohesin's Sccl subunit at the metaphase to anaphase transition is essential for sister chromatid separation and depends on a conserved protein called separin [16].
• Mutations in the Drosophila mei-S332 gene cause premature separation of the sister chromatids in late anaphase of meiosis I [17].
• Centromeres move apart at the metaphase-anaphase transition and Cyclin B is degraded, but sister chromatids remain connected, resulting in chromatin bridging [18].
• Cohesion between sister chromatids during G2 and M phases depends on the "cohesin" protein Scc1p (Mcd1p) [19].

Anatomical context of Chromatids

• p93dis1, which is required for sister chromatid separation, is a novel microtubule and spindle pole body-associating protein phosphorylated at the Cdc2 target sites [20].
• Mutagen sensitivity was assessed by quantitating bleomycin- and benzo[a]pyrene diol epoxide (BPDE)-induced chromatid breaks in peripheral blood lymphocyte cultures [21].
• The frequency of chromatid breakage induced by 1-beta-D-arabinofuranosylcytosine was decreased when hamster cell fibroblasts were treated with chemical agents that interferred with DNA synthesis immediately before addition of the analog [22].
• Human B-cells (CCRF-SB) and normal T-lymphocytes (NTL) readily incorporated [3H]CDR, [3H]TDR, and tritiated 5-bromodeoxyuridine, and they clearly exhibited differential staining of the sister chromatids (SCD) [23].
• Differential chromatid damage induced by 6-thioguanine in CHO cells [24].

Associations of Chromatids with chemical compounds

• We speculate that this self-recognition of guanine-rich motifs of DNA serves to bring together, and to zipper up in register, the four homologous chromatids during meiosis [25].
• We show here that H2AX serine 139 enforces efficient homologous recombinational repair of a chromosomal double-strand break (DSB) by using the sister chromatid as a template [26].
• RESULTS: Our results showed no evidence for the influence of a shared family environment on bleomycin-induced chromatid breaks [27].
• Ara-C differed from caffeine in its effects; whereas both agents increased the frequency of chromatid breaks and gaps, only ara-C increased the frequency of gaps to the level observed in the irradiated malignant cells [28].
• 1-beta-D-arabinofuranosylcytosine-induced chromatid breakage: effect of inhibition of DNA synthesis [22].

Gene context of Chromatids

• We show that destruction of Pds1p is the APC's sole role in triggering Scc1p's dissociation from chromatids and that Pds1p forms a stable complex with a 180 kDa protein called Esp1p, which is essential for the dissociation of Scc1p from sister chromatids and for their separation [19].
• CDC23 is required at the metaphase/anaphase transition to separate sister chromatids, and we speculate that it might promote proteolysis of proteins that hold sister chromatids together [29].
• Here we show that XRCC2 is essential for the efficient repair of DNA double-strand breaks by homologous recombination between sister chromatids [30].
• Higher levels of nondegradable PIM, as well as overexpression of wild-type PIM, inhibit sister chromatid separation [31].
• A functional Rad53 checkpoint kinase that is known to protect the integrity of the sister chromatid junctions is required for the accumulation of recombination intermediates in sgs1 mutants [32].

Analytical, diagnostic and therapeutic context of Chromatids

• Here we evaluate this hypothesis using time-lapse confocal microscopy to visualize, in real time, kinetochore and chromatid movements in living Drosophila embryos in the presence and absence of specific inhibitors of cytoplasmic dynein [33].
• A lagging chromosome seen during anaphase in control or nocodazole-treated cells was found by confocal immunofluorescence microscopy to be a single chromatid with its kinetochore attached to kinetochore microtubule bundles extending toward opposite poles [34].
• Using in situ hybridization of an alpha centromeric probe (alpha R1), which hybridizes to 9 of the 22 human autosomes, we were able to infer that most, if not all, of the micronuclei contain whole chromosomes or chromatids [35].
• No influence of p53 genotype on sister chromatid exchange or G2 chromatid damage was observed in mitogen-stimulated spleen cell cultures; however, a p53 effect on postirradiation mitotic entry was seen [36].
• First, Western blot analysis demonstrated that the levels of two proteins involved in regulating sister chromatid separation and the spindle checkpoint, Mad2 and separase (ESPL1) were increased in null compared with WT cells [37].

References