Collaboration and coordination between Homologous Recombination (HR) and Translesion DNA Synthesis (TLS) factors during the replication of UV-damaged DNA

VALLERGA MB, MANSILLA SF, FEDERICO MB, HABIF M, GONZÁLEZ BESTEIRO M, BERTOLÍN A AND V. GOTTIFREDI.

Montevideo

Conferencia; 1st Conference of the South American Chapter of the Cell Stress Society International.; 2014

Cell Stress Society International.

Collaboration and coordination between Homologous Recombination (HR) and Translesion DNA Synthesis (TLS) factors during the replication of UV-damaged DNA Vallerga MB, Mansilla SF, Federico MB, Habif M, González Besteiro M, Bertolín A and V. Gottifredi Cell Cycle and Genomic Stability Laboratory, Fundación Instituto Leloir-CONICET, Buenos Aires, Argentina .E-mail: vgottifredi@leloir.org.ar When DNA is damaged by UV irradiation, cycling cells face the challenge of replicating damaged-DNA. Replicative DNA polymerases are blocked by UV-triggered DNA lesions and cells activate tolerance mechanisms to avoid the permanent stalling and collapse of replication forks. The best characterized tolerance mechanism is TLS (Translesion DNA Synthesis), a pathway that utilizes alternative DNA polymerases capable of using DNA lesions as replication templates. Another tolerance mechanism that might contribute to DNA replication after UV damage is template switching. This pathway utilizes the newly replicated DNA in the sister chromatid as an alternative template. While TS is not triggered by double strand breaks (DSBs), it requires the participation of classic Homologous Recombination (HR) factors. The contribution of TS to the replication of UV-triggered DNA lesions is yet poorly characterized. Nucleolytic degradation of newly synthesized DNA and the reversal of replication forks might also impact on the speed of fork elongation when DNA is damaged. While these events might be coordinated with DNA damage tolerance events, their level of collaboration is poorly understood. In this talk I will discuss data suggesting strong collaboration of TLS and HR factors in the elongation of replicating forks after UV irradiation.