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+[[!meta title="Mechanisms of insertions at a DNA double-strand break."]]
+[[!tag variants]]
+
+Min J, Zhao J, Zagelbaum J, Lee J, Takahashi S, Cummings P, Schooley A, Dekker J, Gottesman ME, Rabadan R, Gautier J. 
+
+Mol Cell. 2023 Jul 20;83(14):2434-2448.e7. doi: 10.1016/j.molcel.2023.06.016
+
+Mechanisms of insertions at a DNA double-strand break.
+
+[[!pmid 37402370 desc="Indel-seq: double-strand breaks are induced with the
+AsiSI endonuclease or CRISPR, and a target locus is studied by targeted
+sequencing of PCR amplicons.  “the median size of inserts is 120 bp [...] 39%
+of inserts originate from repetitive sequences, including telomeres,
+centromeres, Alu, and retrotransposon elements”  “Inhibition [with NU7441] of
+DNA-PK catalytic activity [involved in NHEJ] significantly decreased insertion
+events. In contrast, the size and number of deletions increased.”  “POLQ
+inhibition did not reduce [...] insertions, indicating that insertions were
+largely independent of microhomology-mediated end joining (MMEJ)”  “Treatment
+with CK-666, a small-molecule inhibitor that stabilizes the Arp2/3 complex in
+an inactive conformation, resulted in a significant decrease in insertion
+events originating from AsiSI-proximal donor sequences”  “siRNA-mediated
+downregulation of RAD51 did not affect the overall number of insertions but
+dramatically [increased] distal (class 3) insertions”.  “8.7% of insertions
+originated from multiple genomic loci on different chromosomes”  “more than 70%
+of donor sequences originated from promoters and transcribed gene body regions”
+“Donor sequences are spread around the AsiSI sites and span the TSS; however,
+insertions preferentially originate from the transcribed side [...]. In
+contrast, donor sequences originating from AsiSI-cleaved DSBs within a gene
+body or distal intergenic regions did not show any bias”  ”[Insertions in] a
+Cas9 DSB near the TSS of the BCL6 locus in a [the OCI-Ly7 cell line] were
+markedly enriched in the direction of transcription.”  “alpha-amanitin
+decreased the frequency of insertions, preferentially those originating from
+promoter-proximal DSBs [...]. Furthermore, donor sequences in
+alpha-amanitin-treated cells were no longer preferentially derived from the
+transcribed side.” “[Upregulating transcription of telomeric repeat-containing
+RNA at telomerse via] FANCM downregulation resulted in a significant increase
+in telomeric insertions.”  “RNA-DNA hybrid disruption by RNaseH1 suppressed the
+bias of donor sequences that originate preferentially from the direction of
+transcription”"]]

diff --git a/tags/variants.mdwn b/tags/variants.mdwn
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@@ -83,6 +83,12 @@ the same transposon participate in an aberrant transposition event to a new
 site”.  They give an example where the two transposons are identical copies
 on sister chromatids in G2 phase.
 
+## Indels
+
+Indel-seq ([[Min and coll., 2023|biblio/37402370]]) shows insertions at
+double-strand breaks originating from donor regions possibly single-stranded by
+transcription (R-loops) or repair.  Proximity and contact appear to be important.
+
 ## Software
 
  - _NanoSV_ ([[Cretu Stancu and coll., 2017|biblio/29109544]]) uses nanopore long