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Heterochromatic DNA Double Strand Break Repair


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Title: Heterochromatic DNA Double Strand Break Repair
Authors: Goodarzi A. Aaron / Noon T. Angela / Jeggo A. Penny
Issue Date: Mar-2009
Citation: Acta medica Nagasakiensia, 53(supl.), pp.13-17 ; 2009
Abstract: Eukaryotic chromatin is segregated into highly condensed heterochromatin and comparably relaxed euchromatin. Although heterochromatic gene expression is either transiently or permanently impeded, the integrity of heterochromatic DNA is critical for cell survival as it contributes to the regulation of nuclear architecture, gene expression, ribosome biogenesis, chromosome stability and mitosis. Formed by a plethora of proteins, structurally complex heterochromatin is generally inaccessible to DNA processing enzymes, including those repair factors required to rejoin DNA double strand breaks (DSBs). To be repaired, heterochromatic lesions require the Ataxia Telangiectasia Mutated (ATM) pathway to transiently modify heterochromatic factors surrounding the DSB, relaxing its structure and thereby allowing DNA non-homologous end-joining (NHEJ) to function. Cells deficient for ATM or proteins involved in its signalling cascade repair euchromatic DSBs normally but are unable to resolve lesions within heterochromatin. Depletion of key heterochromatic proteins, including the KAP-1 transcriptional co-repressor, Heterochromatin Protein 1 (HP1) or histone deacetylases 1&2 (HDAC1&2), relieves the requirement for ATM signalling in DSB repair. Importantly, KAP-1 is a highly dose dependent, transient and specific substrate of ATM and the manipulation of KAP-1 phosphorylation regulates heterochromatic DSB repair. We propose that KAP-1 is a critical heterochromatic factor that undergoes specific modifications following DSB formation to promote repair in a manner that allows localised and transient chromatin relaxation but precludes widespread dismantling of the heterochromatic superstructure.
Keywords: DNA double-strand breaks / Repair / Heterochromatin
URI: http://hdl.handle.net/10069/21793
ISSN: 00016055
Relational Links: http://joi.jlc.jst.go.jp/JST.JSTAGE/amn/53.S13
Type: Departmental Bulletin Paper
Text Version: publisher
Appears in Collections:Volume 53, Supplement

Citable URI : http://hdl.handle.net/10069/21793

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