Bubble harp3/2/2023 We utilized unique genetic tools in Drosophila melanogaster to test whether the fly ortholog of SMARCAL1, Marcal1, mediates annealing during SDSA. We hypothesized that annealing during SDSA is performed by the annealing helicase SMARCAL1, which can anneal RPA-coated single DNA strands during replication-associated DNA damage repair. Despite the central role for SDSA in genome stability, little is known about the defining step: annealing. SDSA has also been proposed to be the primary mechanism for integration of large insertions during genome editing with CRISPR/Cas9. SDSA is the first defense against genomic rearrangements and information loss during DSB repair, making it a vital component of cell health and an attractive target for chemotherapeutic development. DSBs are repaired using end-joining or homology-directed repair strategies, with the predominant form of homology-directed repair being synthesis-dependent strand annealing (SDSA). If repaired incorrectly, they can cause mutations and chromosome rearrangements. If unrepaired, they can lead to chromosome fragmentation and cell death. In this review, we examine how these proteins function, concentrating on their common and unique attributes and regulatory mechanisms.ĭNA double-strand breaks (DSBs) pose a serious threat to genomic integrity. Inherited mutations in SMARCAL1 cause a severe developmental disorder and mutations in ZRANB3 and HLTF are linked to cancer illustrating the importance of these enzymes in ensuring complete and accurate DNA replication. Regulation ensures these powerful activities remain controlled and restricted to damaged replication forks. Remodeling reactions include fork reversal and branch migration to promote fork stabilization, template switching, and repair. The SRD provides specificity to DNA structures like forks and junctions and confers DNA remodeling activity to the motor domains. These proteins are recruited to replication forks through protein–protein interactions and bind DNA using both their motor and substrate recognition domains (SRDs). SMARCAL1, ZRANB3, and HLTF are three related members of this family with specialized functions that maintain genome stability during DNA replication. We hypothesize that loss of SMRC-1 activity causes chronic replication stress, in part because of insufficient recruitment of MET-2 to nuclei.Ī large number of SNF2 family, DNA and ATP-dependent motor proteins are needed during transcription, DNA replication, and DNA repair to manipulate protein–DNA interactions and change DNA structure. Genetic data are consistent with MET-2 and SMRC-1 functioning together to limit replication stress in the germ line and in parallel to promote other germline processes. In the absence of SMRC-1, germline H3K9me2 generally decreases after multiple generations at high culture temperature. MET-2 and SMRC-1 localize to mitotic and meiotic germline nuclei, and SMRC-1 promotes an increase in MET-2 abundance in mitotic germline nuclei upon replication stress. SMRC-1 limits accumulation of DNA damage and promotes germline and embryonic viability. ![]() SMRC-1, like its mammalian ortholog SMARCAL1, provides protection from DNA replication stress. We used molecular, genetic, and biochemical methods to investigate the biological role of SMRC-1 and to explore its relationship with MET-2. elegans histone methyltransferase responsible for H3K9me1 and me2 deposition. Here we report that a conserved DNA repair protein, SMRC-1, associates with MET-2, the C. bhp files created with this app will load on both Mac and iOS versions.Histone modifications regulate gene expression and chromosomal events, yet how histone-modifying enzymes are targeted is poorly understood. Rated #1 Music App and Apple's Top Music App in many countries, since its release. Now it’s available as a Mac application that also makes music. Bubble Harp was first released as a work of interactive art by Scott Sona Snibbe that was only available in galleries and museums. Through the pop-up control panel at the screen’s bottom, you can change from single points to streams of points, change graphic and sonic parameters, and load and save files. You can record long movements of a single point, or stream many points out of your cursor like ink. It’s a combination of drawing, animation, music, art, geometry, and gaming. ** #1 Music App in Mac App Store Worldwide ** iTunes Top 10 App of the Year for Art and Music on iOS **īubble Harp draws bubbles around your mouse’s strokes, recording and replaying your movements while creating music. ![]() "Of the millions of apps out there, none quite capitalize on the sheer fun and beauty of interactivity the way that Scott Snibbe’s do.” -CoolHunting
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