The ACF1 Complex Is Required for DNA Double-Strand Break Repair in Human Cells Mol Cell Dec 22;40(6):976-87

DNA double-strand breaks (DSBs) repair Introduction - DSBs Nonhomologous end-joining (NHEJ) Homologous recombination (HR) broken DNA ends are rejoined without the use of homology Use of homology between the sequences of broken and undamaged DNA strands

Introduction - DSBs DNA double-strand breaks (DSBs) repair Chromatin remodeling factors - SWI/SNF - INO80/SWR - NuRD (CHD) - ISWI ISWI family - ACF complex : ACF1 and SNF2H - CHRAC complex : CHRAC15 and 17 facilitate repair of DSBs

Accumulation of ACF1 and SNF2H at laser-irradiated site Chromatin remodeling factor ACF1 and SNF2H is accumulated at laser-irradiated site Figure 1.

Domains of ACF1 and SNF2H required for the damage response Figure 1. ACF1 N-terminal domains accumulated at damaged site. SNF2H C-terminal domains accumulated at damaged site.

Visualization of NHEJ and ACF protein at DSBs Figure 2. Construction of induced DSBs cell line.

Visualization of NHEJ and ACF protein at DSBs Figure 2. ACF1, SNF2H and KU70/80 are colocalized

Interaction of ACF1 and SNF2H Figure 3. ACF1 and SNF2A suppression does not influence the expression of each other. ACF1/SNF2A suppression makes cells that extremely sensitive to DSBs inducing factors

Interaction of ACF1 and SNF2H Figure 3. ACF1 and SNF2H suppression affects the rapid repair of DSBs. ACF1 is mainly involved in the same DNA repair pathway as KU80.

Influence of ACF1 and SNF2H depletion on NHEJ and HR of DSBs Figure 4. ACF1 and SNF2H are required for efficient NHEJ and HR

Accumulation of KU at DSBs depends on ACF1 Figure 5. ACF1 plays a more important role in KU protein accumulation at DSBs ATPase activity of SNF2H is required for NHEJ of DSBs

Physical association between KU and chromatin remodeling factors Figure 5.

Discussion SNF2H and ACF1 as an ACF complex plas a major role in NHEJ. Chromatin-remodeling factors and chromatin remodeling are important for DSB repair in human cells. Protein-protein interactions within chromatin-remodeling factor complexes and between the remodeling factors/KU proteins may be one of the earliest steps in the response to DSBs