The ACF1 Complex Is Required

for DNA Double-Strand Break Re-

pair

in Human CellsMol Cell. 2010 Dec 22;40(6):976-87

DNA double-strand breaks (DSBs) repair

Introduction - DSBs

Nonhomologous end-join-ing

(NHEJ)

Homologous recombination(HR)

broken DNA ends

are rejoined with-

out the use of

homology

Use of homology

between the se-

quences of bro-

ken and undam-

aged 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-irradi-ated 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 re-pair 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 remodel-ing 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 pro-

teins may

be one of the earliest steps in the response to DSBs