DNA in cells is predominantly B-form double helix. Though certain DNA sequences in vitro may fold into other structures, such as triplex, left-handed Z form, or quadruplex DNA, the stability and prevalence of these structures in vivo are not known. Here, using computational analysis of sequence motifs, RNA polymerase II binding data, and genome-wide potassium permanganate-dependent nuclease footprinting data, we map thousands of putative non-B DNA sites at high resolution in mouse B cells. Computational analysis associates these non-B DNAs with particular structures and indicates that they form at locations compatible with an involvement in gene regulation. Further analyses support the notion that non-B DNA structure formation influences the occupancy and positioning of nucleosomes in chromatin. These results suggest that non-B DNAs contribute to the control of a variety of critical cellular and organismal processes.
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http://dx.doi.org/10.1016/j.cels.2017.01.013 | DOI Listing |
In eukaryotes, mismatch repair begins with M ut S h omolog (MSH) complexes, which scan newly replicated DNA for mismatches. Upon mismatch detection, MSH complexes recruit the PCNA- stimulated endonuclease Mlh1-Pms1/PMS2 (yeast/human), which nicks the DNA to allow downstream proteins to remove the mismatch. Past work has shown that although Mlh1-Pms1 is an ATPase and this activity is important , ATP is not required to nick DNA.
View Article and Find Full Text PDFNucleic Acids Res
December 2024
Department of Biology, Tufts University, Suite 4700, 200 Boston Ave, Medford, MA 02155, USA.
Long AT repeat tracts form non-B DNA structures that stall DNA replication and cause chromosomal breakage. AT repeats are abundant in human common fragile sites (CFSs), genomic regions that undergo breakage under replication stress. Using an in vivo yeast model system containing AT-rich repetitive elements from human CFS FRA16D, we find that DNA polymerase zeta (Pol ζ) is required to prevent breakage and subsequent deletions at hairpin and cruciform forming (AT/TA)n sequences, with little to no role at an (A/T)28 repeat or a control non-structure forming sequence.
View Article and Find Full Text PDFbioRxiv
December 2024
Department of Biology, Penn State University, University Park, PA 16802, USA.
Non-canonical (non-B) DNA structures-e.g., bent DNA, hairpins, G-quadruplexes, Z-DNA, etc.
View Article and Find Full Text PDFOpen Life Sci
November 2024
The First Affiliated Hospital of Huzhou University, Hu Zhou, China.
Radiotherapy is a cornerstone in the treatment of various tumors, yet radioresistance often leads to treatment failure and tumor recurrence. Several factors contribute to this resistance, including hypoxia, DNA repair mechanisms, and cancer stem cells. This review explores the diverse elements that drive tumor radiotherapy resistance.
View Article and Find Full Text PDFGenomics Inform
November 2024
Department of Biotechnology, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur, Andhra Pradesh, 522302, India.
The untranslated regions (UTRs) of genes significantly impact various biological processes, including transcription, posttranscriptional control, mRNA stability, localization, and translation efficiency. In functional areas of genomes, non-B DNA structures such as cruciform, curved, triplex, G-quadruplex, and Z-DNA structures are common and have an impact on cellular physiology. Although the role of these structures in cis-regulatory regions such as promoters is well established in eukaryotic genomes, their prevalence within UTRs across different eukaryotic classes has not been extensively documented.
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