%0 Journal Article %A Jung-Hoon Yoon %A Debashree Basu %A Karthi Sellamuthu %A Robert E Johnson %A Satya Prakash %A Louise Prakash %T A novel role of DNA polymerase λ in translesion synthesis in conjunction with DNA polymerase ζ %D 2021 %R 10.26508/lsa.202000900 %J Life Science Alliance %P e202000900 %V 4 %N 4 %X By extending synthesis opposite from a diverse array of DNA lesions, DNA polymerase (Pol) ζ performs a crucial role in translesion synthesis (TLS). In yeast and cancer cells, Rev1 functions as an indispensable scaffolding component of Polζ and it imposes highly error-prone TLS upon Polζ. However, for TLS that occurs during replication in normal human cells, Rev1 functions instead as a scaffolding component of Pols η, ι, and κ and Rev1-dependent TLS by these Pols operates in a predominantly error-free manner. The lack of Rev1 requirement for Polζ function in TLS in normal cells suggested that some other protein substitutes for this Rev1 role. Here, we identify a novel role of Polλ as an indispensable scaffolding component of Polζ. TLS studies opposite a number of DNA lesions support the conclusion that as an integral component, Polλ adapts Polζ-dependent TLS to operate in a predominantly error-free manner in human cells, essential for genome integrity and cellular homeostasis. %U https://www.life-science-alliance.org/content/lsa/4/4/e202000900.full.pdf