title: Buried territories: heterochromatic response to DNA double-strand breaks.
abstract: Cellular response to DNA double-strand breaks (DSBs), the most deleterious type of DNA damage, is highly influenced by higher-order chromatin structure in eukaryotic cells. Compared with euchromatin, the compacted structure of heterochromatin not only protects heterochromatic DNA from damage, but also adds an extra layer of control over the response to DSBs occurring in heterochromatin. One key step in this response is the decondensation of heterochromatin structure. This decondensation process facilitates the DNA damage signaling and promotes proper heterochromatic DSB repair, thus helping to prevent instability of heterochromatic regions of genomes. This review will focus on the functions of the ataxia telangiectasia mutated (ATM) signaling cascade involving ATM, heterochromatin protein 1 (HP1), Krüppel-associated box (KRAB)-associated protein-1 (KAP-1), tat-interacting protein 60 (Tip60), and many other protein factors in DSB-induced decondensation of heterochromatin and subsequent repair of heterochromatic DSBs. As some subsets of DSBs may be repaired in heterochromatin independently of the ATM signaling, a possible repair model is also proposed for ATM-independent repair of these heterochromatic DSBs.
authors.affiliation: Key Laboratory of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China Institute of Translational Medicine, Zhejiang University, Hangzhou 310029, China.
authors.forename: Yi-Li
authors.initials: YL
authors.lastname: Feng
authors.affiliation: Key Laboratory of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China Institute of Translational Medicine, Zhejiang University, Hangzhou 310029, China.
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Xiang
authors.affiliation: Key Laboratory of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China Institute of Translational Medicine, Zhejiang University, Hangzhou 310029, China.
authors.forename: Na
authors.initials: N
authors.lastname: Kong
authors.affiliation: Key Laboratory of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China cxjzu@hotmail.com anyongxie@zju.edu.cn.
authors.forename: Xiu-Jun
authors.initials: XJ
authors.lastname: Cai
authors.affiliation: Key Laboratory of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China Institute of Translational Medicine, Zhejiang University, Hangzhou 310029, China cxjzu@hotmail.com anyongxie@zju.edu.cn.
authors.forename: An-Yong
authors.initials: AY
authors.lastname: Xie
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D006570:Heterochromatin / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D006570:Heterochromatin; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: DNA damage response; DNA double-strand breaks; DSB repair; decondensation; heterochromatin