tailieunhanh - Báo cáo khoa học: Histone H2A phosphorylation in DNA double-strand break repair

DNA repair must take place within the context of chromatin, and it is therefore not surprising that many aspects of both chromatin components and proteins that modify chromatin have been implicated in this process. One of the best-characterized chromatin modification events in DNA-dam-age responses is the phosphorylation of the SQ motif found in histone H2A or the H2AX histone variant in higher eukaryotes. This modification is an early response to the induction of DNA damage, and occurs in a wide range of eukaryotic organisms, suggesting an important conserved func-tion | FEBS Journal REVIEW ARTICLE Histone H2A phosphorylation in DNA double-strand break repair Elinor R. Foster and Jessica A. Downs Department of Biochemistry Cambridge University UK Keywords chromatin DNA repair H2AX histone H2A Correspondence J. A. Downs Department of Biochemistry Cambridge University 80 Tennis Court Road Cambridge CB2 1GA UK Fax 44 1223 766 002 Tel 44 1223 333 663 E-mail jad32@ Received 11 February 2005 revised 4 April 2005 accepted 28 April 2005 doi DNA repair must take place within the context of chromatin and it is therefore not surprising that many aspects of both chromatin components and proteins that modify chromatin have been implicated in this process. One of the best-characterized chromatin modification events in DNA-dam-age responses is the phosphorylation of the SQ motif found in histone H2A or the H2AX histone variant in higher eukaryotes. This modification is an early response to the induction of DNA damage and occurs in a wide range of eukaryotic organisms suggesting an important conserved function. One function that histone modifications can have is to provide a unique binding site for interacting factors. Here we review the proteins and protein complexes that have been identified as H2AS129ph budding yeast or H2AXS139ph human binding partners and discuss the implications of these interactions. DNA repair must by definition occur within the context of chromatin. The most basic unit of chromatin is the nucleosome consisting of two copies of each of four core histones around which DNA is wrapped in two left-handed superhelical turns 1 . This level of DNA compaction often referred to as beads on a string can be folded into numerous higher-order levels of chromatin condensation 2 . The shift towards more condensed structures is facilitated by the presence of the linker histone 2 . This packaging of DNA while essential for compressing a very long highly negatively charged molecule into a