Collaboration and coordination between tolerance and checkpoint pathways

MARÍA BELÉN VALLERGA; SABRINA F. MANSILLA; MARÍA BELÉN FEDERICO; JULIANA SPERONI; MARTÍN HABIF; VANESA GOTTIFREDI

Foz do Iguacu

Congreso; ICEM 2013-11th International Conference on Enviromental Mutagens. 3rd to 8th November 2013-Foz do Iguacu, PR, Brazil; 2013

International Association of Environmental Mutagens Societies-Brazilian and Latin American Association of Environmental Mutagenesis, Carcinogenesis and Teratogenesis

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 different mechanisms to avoid the permanent stalling and collapse of replication forks. At least in the context of UV triggered lesions, the utilization of permissive DNA polymerases to maintain fork elongation represents an important strategy undertaken during the cellular response to UV light. In fact,the utilization of such alternative DNA polymerases during Translesion DNA Synthesis (TLS) across damaged DNA seems to represent the first line of defense, since defects in the level of expression of the TLS-pol eta impairs genomic stability after UV irradiation. Other mechanisms activated to tolerate DNA damage and/or to avoid fork collapse are also essential for the survival of genomically stable cells after UV challenge. The best characterized TLS-independent auxiliary mechanisms are checkpoint and template switching. While the checkpoint is required to stabilize stall forks and to avoid origin firing, the template switching promotes the elongation of stalled replication forks in a manner that depends on the homology between newly replicated strands. While these pathways have been characterized individually, the level of collaboration between them is currently poorly understood. In this talk I will discuss data suggesting strong collaboration of checkpoint and template switching factors for the onset of TLS events.