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Bloom Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
As a DNA helicase distributed diffusely throughout the nucleus, BLM participated in the maintenance of the fork stability, separation of the DNA duplex into ssDNA substrate, regulation of nucleoprotein filaments, involvement of the synthesis-dependent strand annealing pathway to repair DSB, disentanglement of under-replicated DNA strands during metaphase, handling of unusual DNA structures, and keeping of genome stability. Specifically, by traversing along ssDNA in a 3′ to 5′ direction and breaking the hydrogen bonds that hold the two DNA strands together, BLM opens (unwinds) DNA and facilitates DNA replication and repair, RNA transcription, homologous recombination, and genomic stability [10–13].
Saccharomyces cerevisiae
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Brunella Posteraro, Gianluigi Quaranta, Patrizia Posteraro, Maurizio Sanguinetti
S. cerevisiae is primarily unicellular, although capable of polarized growth (resembling hyphae), by which the cell can grow toward an environmental cue source.17 Its cells come in three types, called a, α, and a/α, and these cell types differ at the mating-type locus that specifies cell type. The two haploid cell types of yeast (a and α) are able to interconvert through a reversible, programmed DNA-rearrangement process known as mating-type switching.18 This process—that could also be called cell-type switching—is indispensable for unicellular organisms such as yeasts that do not contain distinct germline and somatic DNA, and it is reminiscent of the reversible rearrangements that include the shuffling of variant surface glycoprotein genes in kinetoplastids19 and phase variation in Salmonella20—both are microbial strategies to evade the host immune system. Similarly to as in S. pombe, the switching mechanism in S. cerevisiae requires the haploid genome to have one active and two silent copies of the mating-type locus (a three cassette structure). During switching, the active locus is cleaved, and a synthesis-dependent strand annealing process allows it to be replaced with a copy of a silent locus encoding the opposite mating-type information. Consequently, a haploid a cell can become a haploid α cell, or vice versa, by changing its genotype at the mating-type locus.18
Roles of homologous recombination in response to ionizing radiation-induced DNA damage
Published in International Journal of Radiation Biology, 2023
Jac A. Nickoloff, Neelam Sharma, Christopher P. Allen, Lynn Taylor, Sage J. Allen, Aruna S. Jaiswal, Robert Hromas
HR comprises conservative, RAD51-dependent, and non-conservative, RAD51-independent repair mechanisms. RAD51-dependent HR generally results in accurate repair and gene conversion. Two RAD51-dependent DSB repair mechanisms have been proposed, one that involves one strand invasion into a homologous donor duplex, termed synthesis-dependent strand annealing (SDSA), and a second in which both ends invade, producing double-HJ structures, often denoted by the generic term ‘DSB repair’ (Figure 2(A)). Nonconservative HR, termed single-strand annealing (SSA) is RAD51-independent, but requires the ssDNA annealing function of RAD52 (Bhargava et al. 2016). SSA can operate when interacting homologous sequences are linked in direct orientation, so-called ‘direct repeats’ (Figure 2(B)). SSA can also mediate translocations if interacting repeats are on different chromosomes, as shown with nuclease-induced DSBs in mammalian cells (Elliott et al. 2005) and ionizing radiation in yeast (Argueso et al. 2008). SSA is nonconservative because it deletes one of the repeats, as well as intervening sequences between linked repeats, or causes translocations with unlinked repeats. Defects in RAD51-dependent HR shift repair toward error-prone NHEJ and SSA, which increases genome instability, first shown in BRCA2-defective cells (Tutt et al. 2001).