Naslov
Distinct faces of the Ku heterodimer mediate DNA repair and telomeric functions

Autori
Ribes-Zamora, Albert ; Mihalek, Ivana ; Lichtarge, Olivier ; Bertuch, Alison A

Izvornik
Nature Structural & Molecular Biology (1545-9993) 14 (2007), 4; 301-307

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, ostalo

Ključne riječi
Ku, NHEJ, DNA repair

Sažetak
The Ku heterodimer, comprised of Ku70 and Ku80 subunits, is a conserved complex involved in nonhomologous end-joining (NHEJ). However, it also functions in maintenance of telomeres, chromosome termini normally resistant to end-joining events. To elucidate the spatial organization of these functions, we rationally guided Ku mutagenesis in yeast with real-valued evolutionary trace (rvET). This revealed two ancestrally related alpha-helices: one on the Ku70 surface that is required in yeast for NHEJ, and a second on the Ku80 surface that is required in yeast for telomeric heterochromatin formation. When bound to a DNA end, the surface containing the NHEJ-specific Ku70 helix is oriented toward the DNA terminus, whereas the surface containing the telomeric function-specific Ku80 helix faces inward, toward telomeric chromatin, when bound to a telomere. We propose a 'two-face' model for Ku and that divergent evolution of these faces allowed Ku's dual role in NHEJ and telomere maintenance.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Računarstvo, Biotehnologija, Interdisciplinarne biotehničke znanosti, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA