9.6: Molecular Consequences of Uncorrected DNA Damage
- Page ID
- 88952
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)While bacteria also suffer DNA damage, we will focus here on eukaryotes, since they have evolved the most sophisticated repair mechanisms. Remember that unrepaired DNA damage will be passed on to daughter cells in mitosis and might be passed on to the next generation if the mutation occurs in a germline cell.
Why do I say “might” here?
9.6.1. Depurination
Depurination is the spontaneous hydrolytic removal of guanine or adenine from the #1 carbon of deoxyribose in a DNA strand. Its frequency of five thousand depurinations per cell per day emphasizes the high rate of DNA damage that demands a fix! If not repaired, depurination results in a single base-pair deletion in the DNA of one chromosome after replication, leaving the DNA in the same region of the other chromosome unchanged. Figure 9.17 shows the effects.
The replisome ignores the depurinated nucleotide (an A in this example), jumping to the C in the template DNA. Unrepaired, one new double-stranded DNA will have a deletion, leaving the other new one with no mutation.
9.6.2 Pyrimidine Dimerization
Exposure of DNA to UV light can cause adjacent pyrimidines (commonly thymines; less often, cytosines) on a DNA strand to dimerize. Pyrimidine dimers form at a rate of a bit less than one hundred per cell per day! Uncorrected dimerization results in a two-base deletion in one chromosome, while the other remains unchanged (Figure 9.18, below).
You can predict that the correction of this radiation-induced damage will either involve disrupting the dimers (in this example, thymine dimers) or removing the dimerized bases and replacing them with monomeric bases.
9.6.3 Deamination
Figure 9.19 shows the consequences of deamination to a DNA base sequence.
Deamination is the hydrolytic removal of amino (\(\rm -NH_2\)) groups from guanine (most common), cytosine, or adenine, at a rate of one hundred per cell per day. Deamination does not affect thymine (because it has no amino groups!). Uncorrected deamination results in a base substitution on one chromosome (or in this example, a T-A pair substitution for the original C-G) and no change on the other. Deamination of adenine or guanine results in unnatural bases (hypoxanthine and xanthine, respectively). These are easily recognized and corrected by DNA repair systems. Occasionally, some of the U-A base pairs remain unrepaired.