
Scm3は、DNA損傷応答経路を活性化し、DNA修復を促進する。


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The centromeric protein-A (CENP-A) is an evolutionary conserved histone H3 variant that marks the identity of the centromeres. Several mechanisms regulate the centromeric deposition of CENP-A as its mislocalization causes erroneous chromosome segregation, leading to aneuploidy-based diseases, including cancers. The most crucial deposition factor is a CENP-A specific chaperone, HJURP (Scm3 in budding yeast), which specifically binds to CENP-A. However, the discovery of HJURP as a DDR (DNA damage repair) protein and evidence of its binding to Holliday junctions in vitro indicate a CENP-A-deposition-independent role of these chaperones. In this study, using budding yeast, we demonstrate that Scm3 is crucial for the DDR pathway as scm3 cells are sensitive to DNA damage. We further observe that the scm3 mutant interacts with the rad52 DDR mutant and is compromised in activating DDR-mediated arrest. We demonstrate that Scm3 associates with the DNA damage sites and undergoes posttranslational modifications upon DNA damage. Overall, from this report and earlier studies on HJURP, we conclude that DDR functions of CENP-A chaperones are conserved across eukaryotes. Thus, the revelation that these chaperones confer genome stability in more than one pathway has clinical significance.

### Competing Interest Statement

The authors have declared no competing interest.

Evidence of centromeric histone 3 chaperone involved in DNA damage repair pathway

dna修復経路に関与するセントロメア特異的ヒストン3シャペロンの証拠


DNA修復経路に関与するセントロメア特異的ヒストン3シャペロンの証拠


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BRCA1-BARD1はDNA二本鎖切断の修復に必要なDNA末端処理を直接促進し、一方で複製ストレス下でDNAを保護する。その機能のバランスはRAD51の局在によって決まる。


BRCA1–BARD1 directly promotes double-strand break&nbsp;repair by stimulating long-range DNA end resection pathways.

Mechanism of BRCA1–BARD1 function in DNA end resection and DNA protection - Nature

brca1-bard1の機能メカニズム-dna末端処理とdna保護


BRCA1-BARD1の機能メカニズム:DNA末端処理とDNA保護



FANCD2-FANCI複合体は、DNA二重鎖上を滑走し、一本鎖-二本鎖DNA接合部で特異的に結合することで、DNA損傷部位と停止した複製フォークを認識し、修復と保護を行う。


FANCD2–FANCI is a sliding clamp that diffuses on double-stranded DNA&nbsp;but stalls when it reaches a single-stranded gap, providing a unified molecular mechanism that reconciles the roles of FANCD2–FANCI in the recognition and protection of stalled replication forks.

FANCD2–FANCI surveys DNA and recognizes double- to single-stranded junctions - Nature

dna-クロスリンクの修復と複製フォークの保護における-fancd2-fanci-タンパク質複合体の役割


DNA クロスリンクの修復と複製フォークの保護における FANCD2-FANCI タンパク質複合体の役割



酵母 Saccharomyces cerevisiae Rev7 は、Mre11 ヌクレアーゼと Rad50 ATPase 活性を直接的に阻害することで、相同組換えを抑制し非相同末端結合修復を促進する。


Recent studies in cancer cell lines have shown that the tetrameric Shieldin complex (comprising REV7, SHLD1, SHLD2, and SHLD3) facilitates non-homologous end-joining (NHEJ), while blocking homologous recombination (HR). Surprisingly, several eukaryotic species lack SHLD1, SHLD2 and SHLD3 orthologs, suggesting that Rev7 may leverage an alternative mechanism to regulate the double-strand break (DSB) repair pathway choice. Exploring this hypothesis, we discovered that Saccharomyces cerevisiae Rev7 robustly interacts with the Mre11-Rad50-Xrs2 (MRX) subunits, impedes G-quadruplex DNA synergised, HU-induced toxicity and facilitates NHEJ, while antagonizing HR. We identified a 42-aminoacid C-terminal fragment of Rev7 that was critical for its binding to the subunits of MRX complex, protect rev7Δ cells from G-quadruplex DNA-HU-induced toxicity and promote NHEJ by inhibiting HR, whereas the N-terminal HORMA domain, a conserved protein–protein interaction module, was dispensable. We further demonstrate that the full-length Rev7 impedes Mre11 nuclease and Rad50’s ATPase activities, without affecting the latter’s ATP-binding ability. Notably, we found that Rev7 binds with high affinity and specificity to G-quadruplex structures, as opposed to no binding to mixed-sequence single- and double-stranded DNA. These data uncover unanticipated insights into the functional interaction between the MRX subunits and Rev7, and highlight a mechanism by which it regulates the DSB repair pathway choice between HR and NHEJ in S. cerevisiae .

### Competing Interest Statement

The authors have declared no competing interest.

Saccharomyces cerevisiae Rev7 regulates DSB repair pathway choice through binding and blocking Mre11 nuclease and Rad50 ATPase activities

酵母-saccharomyces-cerevisiae-rev7-は-mre11-ヌクレアーゼと-rad50-atpase-活性を結合および阻害することで二本鎖切断修復経路選択を調節する


酵母 Saccharomyces cerevisiae Rev7 は Mre11 ヌクレアーゼと Rad50 ATPase 活性を結合および阻害することで二本鎖切断修復経路選択を調節する
