Template strand scrunching during DNA gap repair synthesis by human polymerase [lamda]
Family X polymerases such as DNA polymerase {lambda}(Pol {lambda}) are well suited for filling short gaps during DNA repair because they simultaneously bind both the 5{prime} and 3{prime} ends of short gaps. DNA binding and gap filling are well characterized for 1-nucleotide (nt) gaps, but the location of yet-to-be-copied template nucleotides in longer gaps is unknown. Here we present crystal structures revealing that, when bound to a 2-nt gap, Pol {lambda} scrunches the template strand and binds the additional uncopied template base in an extrahelical position within a binding pocket that comprises three conserved amino acids. Replacing these amino acids with alanine results in less processive gap filling and less efficient NHEJ when 2-nt gaps are involved. Thus, akin to scrunching by RNA polymerase during transcription initiation, scrunching occurs during gap filling DNA synthesis associated with DNA repair.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1005868
- Journal Information:
- Nat. Struct. Mol. Biol., Vol. 16, Issue (9) ; 09, 2009; ISSN 1545-9993
- Country of Publication:
- United States
- Language:
- ENGLISH
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