The RSC and INO80 Chromatin-Remodeling Complexes in DNA Double-Strand Break Repair - Progress in Molecular Biology - page 225

The RSC and INO80
Chromatin-Remodeling
Complexes in DNA
Double-Strand Break Repair

Anna L. Chambers and
Jessica A. Downs
MRC Genome Damage and Stability
Centre, University of Sussex, Falmer,
Brighton, United Kingdom

I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 230

II. RSC........................................................................................... 232

A. Subunit Composition and Structure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232

B. Biochemical Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234

C. In Vivo Functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236

D. The Role of RSC in DSBR. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237

III. INO80 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244

A. Subunit Composition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244

B. Biochemical Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245

C. In Vivo Functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246

D. The Role of INO80 in DSBR. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247

E. Human INO80 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252

IV. Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253

References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254

In eukaryotes, DNA is packaged into chromatin and is therefore relatively
inaccessible to DNA repair enzymes. In order to perform efficient DNA repair,
ATP-dependent chromatin-remodeling enzymes are required to alter the chro-
matin structure near the site of damage to facilitate processing and allow access
to repair enzymes. Two of the best-studied remodeling complexes involved in
repair are RSC (Remodels the Structure of Chromatin) and INO80 from
Saccharomyces cerevisiae , which are both conserved in higher eukaryotes.
RSC is very rapidly recruited to breaks and mobilizes nucleosomes to promote
phosphorylation of H2A S129 and resection. INO80 enrichment at a break
occurs later and is dependent on phospho-S129 H2A. INO80 activity at the
break site also facilitates resection. Consequently, both homologous recombi-
nation and nonhomologous end-joining are defective in rsc mutants, while
subsets of these repair pathways are affected in ino80 mutants.