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A double-strand break repair model refers to the various models of pathways that cells undertake to repair double strand-breaks (DSB). DSB repair is an important cellular process, as the accumulation of unrepaired DSB could lead to chromosomal rearrangements, tumorigenesis or even cell death. [ 1 ]
Homology-directed repair (HDR) is a mechanism in cells to repair double-strand DNA lesions. [1] The most common form of HDR is homologous recombination . The HDR mechanism can only be used by the cell when there is a homologous piece of DNA present in the nucleus , mostly in G2 and S phase of the cell cycle .
[48] γH2AX (H2AX phosphorylated on serine 139) can be detected as soon as 20 seconds after irradiation of cells (with DNA double-strand break formation), and half maximum accumulation of γH2AX occurs in one minute. [48] The extent of chromatin with phosphorylated γH2AX is about two million base pairs at the site of a DNA double-strand break.
The MRN complex (MRX complex in yeast) is a protein complex consisting of Mre11, Rad50 and Nbs1 (also known as Nibrin [1] in humans and as Xrs2 in yeast). In eukaryotes, the MRN/X complex plays an important role in the initial processing of double-strand DNA breaks prior to repair by homologous recombination or non-homologous end joining.
At various steps of these recombination processes, heteroduplex DNA (double-stranded DNA consisting of single strands from each of the two homologous chromosomes which may or may not be perfectly complementary) is formed. During meiosis non-crossover recombinants occur frequently and these appear to arise mainly by the SDSA pathway.
ATR is recruited for different forms of damage such as nucleotide damage, stalled replication forks and double strand breaks. ATM is specifically for the damage response to double strand breaks. The MRN complex (composed of Mre11, Rad50, and Nbs1) form immediately at the site of double strand break. This MRN complex recruits ATM to the site of ...
The formation of a bivalent occurs during the first division of meiosis (in the zygotene stage of meiotic prophase 1). In most organisms, each replicated chromosome (composed of two identical sister chromatids [1] [2]) elicits formation of DNA double-strand breaks during the leptotene phase. [3]
These double-stranded breaks are typically caused by radiation, and they can be detrimental to the genome. The breaks can lead to mutations that reposition a chromosome and can even lead to the entire loss of a chromosome. The mutations associated with double-stranded breaks have been linked to cancer and other deadly genetic diseases. [5]